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Biomedical subjects

I W McLean

Publications and source records attributed to I W McLean.

At least 19 recordsLinked to original sources

Totally necrotic choroidal and ciliary body melanomas: associations with prognosis, episcleritis, and scleritis.

PURPOSE: To report associations between prognosis, total tumor necrosis, scleritis, and episcleritis in choroidal and ciliary body melanomas. METHODS: In this retrospective observational histopathologic study, 157 totally necrotic melanomas and 177 melanomas that were not totally necrotic of choroidal and ciliary body were retrieved from the Registry of Ophthalmic Pathology. The eyes were examined for the histologic evidence of inflammatory cells within the sclera and episcleral tissues. Contingency table, Kaplan-Meier, and Cox proportional hazard regression analyses were performed. In the survival analyses, only deaths with metastatic melanoma were considered as events in the statistical analysis. RESULTS: Among the totally necrotic melanomas, 118 of 157 (75.1%) had both episcleritis and scleritis; two of 157 (1.3%) had scleritis only; 29 of 157 (18.5%) had episcleritis only; and eight of 157 (5.1%) had neither episcleritis nor scleritis. Among the non-necrotic melanomas, 23 of 177 (12.9%) had both episcleritis and scleritis; eight of 177 (4.5%) had scleritis only; 71 of 177 (40.1%) had episcleritis only; and 75 of 177 (42.3%) had neither episcleritis nor scleritis. Cox regression indicated that total necrosis and scleritis were prognostically significant (P <.05) when analyzed univariately but not significant when analyzed multivariately with tumor size. CONCLUSIONS: Scleritis and episcleritis were statistically significantly associated with total tumor necrosis. There was a higher incidence of episcleritis than scleritis in both the necrotic and non-necrotic tumor types. Associations with patient outcome were identified for necrosis and scleritis. However, these associations were statistically insignificant when the prognostic effect of tumor size was also considered in a multivariate model.

Choroid Neoplasms↗

Ectopic chordoma with orbital invasion.

PURPOSE: To report a rare ectopic chordoma within the orbital wall. METHODS: Case report. RESULTS: A 63-year-old woman developed swelling of the eyelid, tearing, blurred vision, and progressive proptosis RE of 1 month's duration. Neuroimaging studies revealed an osteolytic mass with epicenter at the sphenozygomatic suture that eroded intracranially, invaded into the orbit, and compressed orbital soft tissues. Surgical debulking was done followed by radiation treatment. The pathologic findings of physaliphorous epithelial cells with multiple vacuoles containing mucin, prominent nuclei, and positive immunohistochemical staining for S-100, Vimentin, epithelial membrane antigen, and pancytokeratin were diagnostic for chordoma. CONCLUSION: Orbital wall ectopic localization of a chordoma distant from the clivus is a rare occurrence.

Biomarkers, Tumor↗

Uveal melanoma: mean of the longest nucleoli measured on silver-stained sections.

PURPOSE: To summarize and compare the various histologic methodologies for using nucleoli to assess the malignant potential of uveal melanoma. METHODS: This was an observational series of 100 samples of uveal melanoma in which histologic sections were studied. The cases were selected so that approximately half (n = 49) of the tumors were from patients who had died of metastatic malignant melanoma. The 51 remaining tumors were from patients who had survived at least 9 years without development of metastasis. Central sections from the uveal melanomas were stained using the colloidal silver nitrate stain for nucleolar organizing regions (AgNOR). These were compared with an adjacent hematoxylin and eosin (H&E)-stained section. A light microscope with a micrometer inset into the eyepiece (x10) was used at a final magnification of x1000 under oil immersion to measure the length of the nucleolus along the longest axis and the width perpendicular to that axis. From at least twenty cells selected from random fields throughout the tumor, the mean of the 10 longest and widest nucleoli (MLN) was calculated. Seven samples had to be discarded because the nucleoli were unmeasurable. RESULTS: T-tests and Cox proportional hazard regression analysis indicated that the MLN of nucleolar length as measured on AgNOR-stained slides was as significant as cell type but was more significant than other histopathologic prognosticating variables measured and evaluated in this study. These prognosticators included tumor size, calculated as the largest tumor dimension; MLN width; and MLN length, as measured on H&E-stained sections. CONCLUSIONS: It has previously been demonstrated that AgNOR-stained nucleoli, unlike H&E-stained nucleoli, can be captured and measured by an automated image analyzer with prognostically significant results. This new method of simple oil-immersion measurements of the longest AgNOR-stained nucleoli length in microscopic sections of uveal melanoma provides an inexpensive and highly significant method for predicting outcome in patients with uveal melanoma. Because of the high contrast with the background, the silver-stained nucleoli clearly define the nucleolar boundaries, rendering them readily discernible and allowing greater ease and speed of measurement when compared with H&E-stained nucleoli. The method of random sampling that was used was comparable with linear sampling in predicting outcome. Highly necrotic tumors, however, had to be excluded from the study because of loss of nucleolar morphology.

Cell Nucleolus↗

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↗

Bilateral necrotizing scleritis and blindness in the myelodysplastic syndrome presumably due to relapsing polychondritis.

PURPOSE: The purpose of this study was to report a case of bilateral blindness, bilateral necrotizing scleritis, and bilateral deafness in a patient with myelodysplastic syndrome (MDS). In such a patient, the possibility of relapsing polychondritis (RPC) associated with MDS must be considered. CASE REPORT/METHODS: A 66-year-old patient suffered from myelodysplastic syndrome (MDS). Shortly before his death, he became bilaterally blind and deaf. A biopsy was taken from the conjunctiva and the bone marrow, and both eyes were obtained after death for further investigation. Findings of the clinical and laboratory work-up for the patient's hematologic disorder as well as an examination of the eyes by light microscopy and immunohistochemistry are presented. RESULTS: Ocular sections showed a diffuse necrotizing scleritis with moderate uveitis and no identifiable infectious agent. Neither was there any evidence of a leukemic infiltration. The deafness had been due to inner ear failure, and the patient died of a cardiac failure. CONCLUSIONS: Non-infectious scleritis associated with inner ear deafness is a strong indication of relapsing polychondritis (RPC). Furthermore, RPC can be associated with MDS. Thus, in addition to leukemic infiltration and infection involving ocular structures, ophthalmologists and otolargyngologists should be aware of the association between MDS and RPC and the potential complications.

Aged↗

Differential diagnosis of the conjunctival melanoses.

The conjunctival melanoses are a group of diseases that share the common clinical findings of flat granular melanin-pigmentation of the conjunctival epithelium. Because differential diagnosis of these lesions is difficult, there is much confusion in the literature regarding taxonomy of these lesions. A histopathologic classification of benign melanosis; primary acquired melanosis with atypia, and primary acquired melanosis with melanoma is proposed. Benign melanosis should be divided based on clinical findings into complexion-associated melanosis, secondary melanosis, ephelis, and primary acquired melanosis without atypia.

Conjunctiva↗

Mixed type basal cell carcinoma of the eyelids.

A retrospective histopathologic review of 97 patients with basal cell carcinoma of the eyelid was performed to determine the prevalence and behavior of tumors with a mixed pattern of growth. A mixed type basal cell carcinoma was defined as a tumor having a significant nodular or ulcerative component combined with an infiltrative component. Histologic classification of the 97 tumors yielded four (4.1%) that were multicentric, 67 (69.1%) that were nodular, one (1%) that was ulcerative, 13 (13.4%) that were infiltrative, and 12 (12.4%) that were the mixed variant. Follow-up was obtained on 8 of the 12 patients with mixed basal cell carcinoma. Three tumors recurred, but there were no tumor-related deaths. One of these patients underwent numerous eyelid resections over a 2-year period and then underwent an orbital exenteration. The authors conclude that mixed type basal cell carcinomas are not infrequent and behave as aggressively as basal cell carcinomas of the morphea type. A greater awareness and recognition of mixed type basal cell carcinomas by ophthalmologists and pathologists should result in fewer recurrences and better patient management.

Adult↗

Mild form of Maroteaux-Lamy syndrome: corneal histopathology and ultrastructure.

PURPOSE: Maroteaux-Lamy syndrome is one of the mucopolysaccharidoses (MPSs) that is caused by the incomplete degradation and storage of dermatan sulfate. METHODS: We describe a 49-year-old female patient with the mild form of the disease (MPS VI-B) who developed bilateral increasing corneal opacification and increased intraocular pressure after cervical-fusion surgery. After treatment of the increased intraocular pressure, she underwent a penetrating keratoplasty of her right eye. RESULTS: The histopathologic and ultrastructural features of the corneal button were the accumulation of membrane-bound vacuoles containing fibrillogranular and lamellated material in keratocytes and endothelial cells and thinning of Descemet's membrane with excrescences. CONCLUSION: Our review of the literature reveals only two prior histologic studies of corneas affected by MPS VI B.

Cervical Vertebrae↗

Uveal melanoma: the importance of large nucleoli in predicting patient outcome--an automated image analysis study.

BACKGROUND: Automated image capture and analysis (AICA) has not previously been used to measure the size of nucleoli in uveal melanoma. In this study, the measurements were tested for a possible association with patient outcome. METHODS: Sections from 63 uveal melanomas were stained using the silver stain for nucleolar organizing regions (AgNOR). AICA was used to measure the following five nucleolar features in ten microscopic fields of the tumor: area, circularity, maximum diameter, width, and length of the perimeter. For each tumor, the mean and standard deviation of each of the features were calculated based on all the nucleoli and on subsets of nucleoli with larger areas. For the five nucleolar features the mean of the largest value (MLV) in each of the ten fields was calculated. For comparison, a related visually measured nucleolar feature (MLN) was obtained from hematoxylin and eosin stained sections using a filar micrometer. RESULTS: Thirty-four patients died with metastatic disease and 29 patients survived at least 5 years without metastasis. A greater proportion of nucleoli larger than 3 mm2 in greatest dimension were from patients who died of their disease. The means of the nucleolar features were less significant outcome discriminators than the standard deviations. Means and standard deviations based on subgroups of nucleoli larger than 3 or 3.5 mm2 in greatest dimension were better discriminators. The MLVs were as effective discriminators as the corresponding standard deviations of the larger nucleoli and were better discriminators than MLN. CONCLUSIONS: AICA of AgNOR stained sections of uveal melanoma provides an excellent method for predicting the outcome of patients with uveal melanoma.

Automation↗

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↗

Adenoid cystic carcinomas of the lacrimal gland in childhood and adolescence.

OBJECTIVE: To see if there is a correlation between histologic features of these tumors and final outcome. DESIGN: A small series of cases of adenoid cystic carcinomas of the lacrimal gland in patients 18 years of age or younger were evaluated. PARTICIPANTS: A total of 11 cases of adenoid cystic carcinoma of the lacrimal gland in patients 18 years of age or younger found in the registry of Ophthalmic Pathology at the Armed Forces Institute of Pathology were studied. INTERVENTION: Histologic material obtained by excision of lacrimal gland tumors was evaluated for different morphologic parameters. Clinical follow-up information was reviewed. MAIN OUTCOME MEASURES: All cases were evaluated for proportion of a basaloid histologic pattern: necrosis, hemorrhage, mitotic count, and perineural, vascular, intraosseous, leptomeningeal, and optic nerve invasion. These parameters were examined for an association with the clinical follow-up that was obtained for eight of the patients (mean follow-up, 10 years; range, 2-14 years). RESULTS: Most of the patients were female (M:F = 2:9). Mean age was 14 years (range, 6.5-18 years). Of the patients with follow-up, 5 (62.5%) of 8 survived. Estimated survival rate at 15 years was 58% (Kaplan-Meier analysis). Survivors had 25% or less basaloid histology. Necrosis, hemorrhage, perineural invasion, and mitotic count were less prominent in survivors than in those who died of disease. Vascular invasion was seen only in fatal cases. CONCLUSIONS: Young patients with adenoid cystic carcinomas have a better prognosis than do adult patients, which may be due to their tumors having less aggressive histologic features.

Adolescent↗

Uveal melanoma. Comparison of the prognostic value of fibrovascular loops, mean of the ten largest nucleoli, cell type, and tumor size.

PURPOSE: This study was performed to determine the prognostic significance of the presence of loops defined as periodic acid-Schiff-positive fibrovascular septa that completely surround lobules of tumor cells in cases of uveal melanoma. METHODS: The presence of loops was evaluated using an ordinary light microscope and routinely stained periodic acid-Schiff and hematoxylin sections from 496 posterior uveal melanomas without knowledge of the follow-up data on the patient. RESULTS: At 15 years, survival decreased from 67.5% to 33.8% when complete loops were present. Univariate Cox regression analysis indicated that the presence of loops was an indicator of poor outcome, and was better than age but not as good as the mean diameter of the largest nucleoli, cell type, or tumor size. CONCLUSIONS: The presence of loops, as evaluated in this study, was not as strong an indicator of poor outcome as were loops assessed in a previous study of 234 cases from another laboratory. The authors suspect this difference may be due to their only using routinely stained sections without a green filter, as was used in previously reported studies. The authors description of loops does not require any special equipment and gives sufficiently useful results to justify its inclusion by the pathologist in reports of such specimens. A description of vascular loops should be added to the use of the modified Callender cell type, tumor dimensions, mitotic count, extraocular extension, and lymphocytic infiltration in the final pathologic report.

Cell Division↗

Adenoid squamous carcinoma of the conjunctiva--a clinicopathological study of 14 cases.

AIMS: In order to determine the clinicopathological features and optimum management of a series of patients with adenoid squamous cell carcinoma of the conjunctiva, all cases of squamous cell carcinoma (SCC) of the conjunctiva and cornea on file in the registry of the ophthalmic pathology at the Armed Forces Institute of Pathology were reviewed. METHODS: On histopathological examination, a predominant adenoid or pseudoglandular pattern due to islands of neoplastic squamous or epidermoid cells surrounded by acantholytic cells was necessary for inclusion in the study. Histochemical and transmission electron microscopic studies (TEM) were performed. Clinical features of all the patients were extracted from the charts. RESULTS: The anatomical location of the 14 tumours was corneoscleral limbus (seven patients) and bulbar conjunctiva (seven patients). Eight patients presented with inflammatory signs and irritation (red eye, tearing, foreign body sensation), while six patients developed a slowly growing, painless mass. Histochemical and TEM studies showed extracellular hyaluronic acid and no intracellular mucin. Of the two patients initially treated by enucleation, one was free of disease after 2 years while the second patient had recurrence in the socket and died of brain metastases despite wide orbital excision and radiotherapy. All five patients with recurrent tumours initially had irritated red eyes and two required enucleation. One such patient, after orbital exenteration and radiotherapy, died of unrelated disease. CONCLUSION: The study demonstrates that adenoid SCC of the conjunctiva often presents with inflammatory signs. The tumour is locally aggressive and may metastasize and should, therefore, be histopathologically differentiated from the less aggressive conventional squamous cell carcinoma. Optimum treatment includes wide excision with documented histological clear margins of resection on permanent sections and frequent follow up.

Adult↗

Primary orbital melanomas.

PURPOSE: Primary orbital melanomas are rare tumors with a poorly defined biologic course. Most recorded experiences concern single case reports. The authors evaluated the applicability of several of the histopathologic prognostic indicators used for uveal melanomas to a series of primary orbital melanomas with known clinical follow-up. METHODS: Twenty-one primary orbital melanomas, each with at least a 1-year follow-up after diagnosis, were evaluated for (1) modified Callender cell type, (2) mitotic count per 40 high-power fields, (3) lymphocyte count (less than versus greater than 100/20 high-power fields), (4) blue nevus component, and (5) largest tumor diameter. RESULTS: All patients for whom race was recorded were white. The mean age at diagnosis was 42 years (range, 15-84 years). There was an associated blue nevus in 19 patients (90 percent), and in 10 patients (47.5 percent) there was some form of congenital melanosis. With a mean follow-up period of 4.5 years (range, 1-13 years), mortality from metastatic tumor occurred in 8 (38 percent) of 21 patients. Of these eight patients, there were liver metastases in seven (88 percent) and brain metastases in one (12 percent). Indicators of poor prognosis were tumors of mixed cell type with high mitotic count and greater patient age with underlying congenital melanosis. CONCLUSION: Most primary orbital melanomas occur in white patients and are associated with blue nevi. These tumors are similar to uveal melanomas with respect to prognostic indicators and pattern of metastasis.

Adolescent↗

Benign orbital fibrous histiocytoma simulating a lacrimal gland tumor.

The case of a patient with a lacrimal fossa mass that was believed to be a primary lacrimal gland tumor is reported. However, at lateral orbitotomy the tumor was found within the lacrimal fossa, but distinct from the lacrimal gland. Histopathology revealed a benign fibrous histiocytoma. The tumor was totally excised, has not recurred over a 3-year follow-up period. This mesenchymal tumor should be included in the differential diagnosis of lacrimal fossa mass in adults.

Adult↗

Choroidal-ciliary body melanoma. A multivariate survival analysis of tumor location.

BACKGROUND: Posterior uveal melanomas with ciliary body involvement have greater mortality when compared with choroidal melanomas. This study was conducted to determine if this association is due to an independent effect or to correlations with other parameters. METHODS: From the 4335 cases of uveal melanoma with follow-up data in the Registry of Ophthalmic Pathology, 664 were selected; therefore, approximately two thirds of the patients died of metastatic melanoma. Ciliary body involvement was determined by the location of the anterior tumor margin. Kaplan-Meier survival, Cox regression, and Gamel-Boag log-normal regression analyses were performed. Covariables included ciliary body involvement, largest tumor dimension, mean diameter of the largest ten nucleoli, and modified Callender classification. RESULTS: Kaplan-Meier and univariate Cox analyses indicated a significant association between ciliary body involvement and tumor-related death but when included in a multivariate Cox model, ciliary body involvement was not statistically significant. Similarly, when ciliary body involvement was included in a multivariate Gamel-Boag model, ciliary body involvement was not statistically significant. Melanomas that involve the ciliary body were more likely to be larger (Student's t = 10.5; P = 10(-6)), contain larger nucleoli (Student's t = 2.43; P = 0.015), and be of mixed cell type (chi-square = 17.2; P = 3 x 10(-5)). CONCLUSIONS: Ciliary body involvement is associated with tumor-related mortality but this association is primarily due to ciliary body tumors being larger with more malignant cytology.

Choroid Neoplasms↗