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Biomedical subjects

I W McLean

Publications and source records attributed to I W McLean.

At least 37 records · Page 2Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

Granulomatous reaction to Bowman's layer in herpetic keratitis and band keratopathy.

OBJECTIVE: To characterize granulomatous reactions around Bowman's layer. DESIGN: Case series. SETTING: Registry of Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington. PATIENTS: All patients with a code for granulomatous reactions to Bowman's (membrane) layer or Descemet's membrane. In addition, all corneas identified as having elastotic or calcific degeneration of Bowman's layer were reexamined to identify a possible granulomatous reaction to Bowman's layer. RESULTS: Review of 210 corneal buttons and enucleated eyes yielded eight cases in which evidence of a granulomatous reaction to Bowman's layer was present: five patients with chronic keratitis, including three with herpetic keratitis (disciform in two and ulcerative in one), and three patients whose corneas had old degenerative pannus with calcification of Bowman's layer. In the patients with chronic keratitis the reaction tended to be focal and accompanied by inflammation; in those with degenerative pannus the reaction was diffuse and accompanied by minimal inflammation. CONCLUSIONS: Granulomatous reactions to Bowman's layer are observed much less frequently than granulomatous reactions to Descemet's membrane. Although the pathogenesis of granulomatous reaction to Bowman's layer is unclear, a change in the antigenic properties of Bowman's layer may be implicated.

Adult↗
PubMed1995

Posterior keratoconus. Case report with scanning electron microscopy.

We report the clinical and scanning electron microscopic findings in an older adult patient with unilateral posterior keratoconus. Clinically, the cornea showed typical posterior concavity with focal underlying anterior ectasia and an epithelial iron ring. Scanning electron microscopy of the cornea removed at penetrating keratoplasty revealed a pericentral posterior concavity. The endothelial layer was intact, with moderate endothelial cell pleomorphism. There were no excrescences of Descemet's membrane or endothelial tags. The lack of discrete irregularities on the posterior corneal surface in this case is different from previous descriptions of the pathological appearance of posterior keratoconus, which have been used to support a relationship of this condition to central corneal mesenchymal dysgenesis. This is the first report of scanning electron microscopic findings in posterior keratoconus.

Aged↗
PubMed1994

A stable, multivariate extension of the log-normal survival model.

When applied to survival data from a population of cancer patients, the log-normal model provides estimates of three important parameters: cured fraction, mean log survival time, and standard deviation log survival time. In the original model, however, these parameters are unrelated to prognostic covariates. Furthermore, the original algorithm is computationally unstable and highly dependent on initial parameter estimates. We have developed an extension of the log-normal model that stabilizes computation and expresses survival parameters as functions of prognostic covariates. We have also developed an ancillary algorithm that provides reliable initial estimates.

Algorithms↗
PubMed1994

Characterization of intraocular tumors arising in transgenic mice.

PURPOSE: To characterize intraocular tumors that arise by in situ transformation in the choroid-retinal pigment epithelium (RPE) in transgenic mice bearing the SV40 oncogene under the control of the mouse tyrosinase promoter. METHODS: Tumors from TySV40 transgenic mice were characterized in vivo and in vitro by immunohistology, compound microscopy, and electron microscopy. Tumor cell lines were established and characterized for growth and metastatic potential in the eyes of nude mice. RESULTS: On light microscopy, ocular tumors were predominantly epithelioid, although occasional clusters of spindle cells were also present. Transmission electron microscopy revealed the presence of numerous basal infoldings and abundant multilaminated basement membranes on the ocular tumors. Tumors stained with antibodies to melanoma-associated antigens, gangliosides GD2 and GD3, and the SV40 T antigen. Radiolabeled transgenic tumor cells preferentially localized in the liver after intravenous injection in normal mice. Intracamerally transplanted transgenic tumors metastasized from the eyes to the livers of nude mice. CONCLUSIONS: In TySV40 transgenic mice, intraocular tumors develop that arise at the choroid-RPE interface, and they display morphologic and ultrastructural features consistent with RPE carcinomas. However, the transgenic tumors express melanoma-associated antigens and a propensity to metastasize to the liver, two features characteristic of uveal melanomas. The TySV40 transgenic murine tumors represent potentially useful tools for investigations into the biology and metastasis of intraocular neoplasms.

Animals↗
PubMed1993

Biologic distinctions between cure and time to death in 2892 patients with intraocular melanoma.

BACKGROUND: For certain types of cancer, resection alone rarely achieves a cure, but patients nevertheless tend to have a prolonged survival before they die of the tumor. For other types of cancer, the opposite scenario prevails, suggesting that those biologic mechanisms that allow a curative resection are not identical to those that determine survival time among uncured patients. METHODS: The multivariate log-normal model can be used to detect the association of cured fraction and median survival time of patients with specific prognostic covariates. This model was applied to survival data from 2892 patients with intraocular melanoma who were treated by enucleation. RESULTS: This analysis showed that large tumor size and pleomorphic nucleoli within the tumor were associated independently with a low probability of cure and short median survival time. Advanced patient age and mixed cell type, however, were highly associated with only a short median survival time. CONCLUSIONS: For patients with intraocular melanoma treated only by enucleation, the median survival time is not modulated by the same biologic factors that determine the likelihood of a curative resection.

Age Factors↗
PubMed1993

The biology of haematogenous metastasis in human uveal malignant melanoma.

Using data on 4726 cases of uveal melanoma collected by the Registry, of Ophthalmic Pathology at the Armed Forces Institute of Pathology, my co-workers and I have been studying the biology of haematogenous metastasis. We have developed methods for evaluating separately the relationships between prognostic factors and cure-rate and median survival time for uncured patients. We have discovered that size of the tumour and size of the largest nucleoli in the cells of the uveal melanomas related equally to cure-rate and median survival time. The presence of Callender's epitheloid-type cells in the tumour and increased patient age had little effect on cure-rate but dramatically reduced the median survival time.

Humans↗
PubMed1993

Assessing the impact of adjuvant therapy on cure rate for stage 2 breast carcinoma.

The log-rank test is commonly used to assess therapeutic effect in prospective, randomised clinical trials. This test is sensitive to differences in survival between treatment groups at a specific endpoint, but cannot determine whether such a difference is due to an enhanced cure rate or an enhanced survival time among uncured patients. To investigate the clinical impact of such limitations, an algorithm was constructed to simulate clinical, randomised, adjuvant therapy trials in patients with a cured fraction of 0.27 and a median survival time for uncured patients of 3.4 years. Hypothetical therapies were introduced to increase rate of cure, increase median survival time, or achieve a combination of these effects. For 500 simulated patients recruited over a 5 year period and then followed for three additional years, a 50% enhancement of median survival time (to 5.1 years) led to a survival increase detectable at the P = 0.05 level in 780 of 1000 trials, whereas a 50% enhancement of cured fraction (to 40.5%) led to a detectable increase at the same level in only 449 of 1000 trials. These findings suggest that, in clinical trials of adjuvant therapy for stage 2 breast cancer, the log rank test may be more sensitive to increases in tumour-related survival time than to increases in cured fraction.

Algorithms↗
PubMed1993

Immunohistochemistry of infiltrating lymphocytes in uveal malignant melanoma.

PURPOSE: To investigate using immunohistochemistry the unusual finding that tumor infiltrating lymphocytes (TIL) in uveal melanomas are associated with a higher mortality rate. METHODS: We performed immunohistochemistry for B and T lymphocytes on 80 uveal malignant melanomas, which previously had been reported to contain more than 100 TIL per 20 high-powered fields. In a second study of 90 patients, we counted the number of immunohistochemically stained T lymphocytes per 20 high-powered fields in uveal melanomas from 30 patients who survived at least 15 years after enucleation, from 30 patients who died with metastasis within 2 years, and from 30 patients who died with metastasis more than 10 years after enucleation. RESULTS: T cells predominated in 73.8% of the 80 patients, and B cells were more prevalent in 13.8%. T cells were usually scattered, and B cells were usually in clumps. Post-enucleation 18-yr mortality from metastasis was 73% for patients with either T- or B-cell predominance of their TIL. The mortality rate was 32% for patients with few TIL. The patients who survived at least 15 yrs after enucleation had fewer T lymphocytes infiltrating their uveal melanomas than the two groups of patients who died with metastasis. CONCLUSIONS: The pattern of the TIL was different for T and B cells in uveal melanomas. T-lymphocytic infiltration is associated with death due to metastasis.

B-Lymphocytes↗
PubMed1992

A comparison of prognostic covariates for uveal melanoma.

For 740 selected cases of uveal melanoma from the Armed Forces Institute of Pathology, the following features were determined: the age and sex of the patient, Callender cell type (CT), and largest tumor dimension (LTD). In addition, special morphometric devices were used to measure the standard deviation of nucleolar area (SDNA) and the mean of the largest nucleoli (MLN) from a single routine hematoxylin and eosin-stained section of each tumor. Univariate analysis using the Cox proportional-hazards model revealed that LTD, CT, SDNA, and MLN correlated equally with death from metastatic melanoma (P greater than 10(-6). Age correlated less highly (P less than 0.002), and sex had no relationship to mortality. Multivariate analysis revealed that adding LTD as a prognostic covariate to either CT, SDNA, or MLN yielded a substantial increase in prognostic value. Because MLN can be measured more easily than SDNA and is more reproducible than CT, it can be a useful cytologic index of the malignant potential of uveal melanomas.

Choroid Neoplasms↗
PubMed1991

Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase.

The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors.

Antibodies, Monoclonal↗
PubMed1991

Phacoanaphylactic endophthalmitis: a clinicopathologic review.

Lens-induced uveitis or phacoanaphylactic endophthalmitis (PE) is a chronic endophthalmitis with a zonal granulomatous inflammation surrounding a ruptured lens. One hundred forty four cases of PE were retrospectively evaluated clinically and histopathologically. The disease was not well recognized clinically as only six of the cases were given the clinical diagnosis of PE. Most cases (80%) occurred after trauma, surgical or non-surgical. The time after injury varied from two days to fifty nine years. Of those individuals less than 55 years of age who had no history of trauma. 29% were noted by clinical history to have microphthalmia. Although classically the inflammation of PE has been described as being confined to the anterior aspect of the eye, the choroid was involved with an inflammatory reaction in 76% of the cases.

Acute Disease↗
PubMed1991

Cutaneous melanoma of the eyelid. Clinicopathologic features.

The authors reviewed the clinical and histopathologic features of 32 patients with cutaneous malignant melanoma of the eyelid. The lower eyelid was more frequently the site of origin than the upper eyelid (21 patients, 66% of cases). A clinical diagnosis of melanoma was made in only 2 of 13 patients (15%) for whom the clinical diagnosis was listed. Clinical findings of pigmentation, ulceration/hemorrhage, or growth were documented in 25 (78%) patients. The histopathologic classification of the melanomas included nodular (19 patients, 59%), superficial spreading (7 patients, 22%), and lentigo maligna (6 patients, 19%). Associated histopathologic findings included solar elastosis (13 patients, 41%), nevus (12 patients, 38%), and basal cell carcinoma (4 patients, 13%). One of eighteen patients with follow-up data available died of metastatic melanoma.

Adult↗