Is primary acquired melanosis of the conjunctiva equivalent to melanoma in situ?
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Biomedical subjects
Publications and source records attributed to I W McLean.
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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.
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.
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.
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.
Two patients who had similar clinical presentations of bilateral multiple chorioretinal lesions and needed a correct diagnosis underwent chorioretinal biopsy. The biopsy from one patient demonstrated mainly a B cell infiltrate in choroidal and subretinal nodules, while the biopsy from the second patient showed mainly macrophages in the retina. These findings directed the therapeutic approach taken in each patient. Although chorioretinal biopsy is an invasive procedure with the potential for serious complications, the resultant finding may aid in the diagnosis and guide the subsequent management of certain patients presenting with serious ocular findings of undefined etiology.
A 21-year-old man with a history of an excised soft tissue mass of the groin and spotty cutaneous pigmentation underwent excision of nodules of the right lower and left upper eyelids. The patient subsequently had a cutaneous mass of the left ear removed. All excised lesions were classified as myxomas. A diagnosis of multiple myxoma, spotty pigmentation, and endocrine overactivity (Carney's) complex was made.
Two features of eyes enucleated for posterior uveal melanoma that may serve as indicators for traumatic enucleation and relate to dissemination of tumor cells at the time of enucleation are myelin artifact of the optic nerve head and acute hemorrhage within the tumor. Myelin artifact occurs when crushed optic nerve tissue is squeezed into the eye at the time of enucleation. Intralesional hemorrhage may occur during surgery and may be correlated with fluctuations in intraocular pressure. We reviewed 519 cases of posterior uveal melanoma treated by enucleation between 1950 and 1970. Without knowledge of the follow-up data, we examined histologic sections for myelin artifact, intralesional hemorrhage, subretinal hemorrhage, Callender cell type, size of tumor, necrosis, and scleral or orbital invasion. Neither myelin artifact nor intralesional hemorrhage were independent prognostic risk factors. These findings do not support or refute the hypothesis that excessive trauma during enucleation results in a worse prognosis.
A randomized controlled clinical trial of methanol-extracted residue of bacille Calmette-Guerin adjuvant treatment of posterior uveal melanoma was undertaken. Of 113 patients, 34 patients received adjuvant immunotherapy and 79 patients received no treatment. No difference in survival was observed between the adjuvant-treated group and the control group of patients. This study found that the size of the tumor was a highly significant risk factor for death caused by metastasis of uveal melanomas. The standard deviation of the nucleolar area of the neoplastic cells was a significant risk factor, even though patients with tumors composed of Callender's spindle-type cells were not included in the study.
We studied the immunohistopathologic features of normal lacrimal gland, benign mixed tumor, and malignant mixed tumor of the lacrimal gland. Primary antisera were to keratin, muscle-specific actin, vimentin, and glial fibrillary acid protein. Keratin stained in occasional myoepithelial cells in normal gland, ductal epithelium in normal gland and the tumors, and occasional stromal epithelioid cells in the tumors. Muscle-specific actin stained in myoepithelium and vascular smooth muscle in normal gland and the tumors, and occasional spindle-shaped and clusters of stromal cells in the tumors. Vimentin staining was nonspecific. Glial fibrillary acid protein stained in occasional myoepithelial cells in normal gland and polyhedral stromal cells in benign mixed tumor. Our findings indicate that ductal epithelium develops into the epithelial component, and some cells in the stroma and myoepithelium develop into some cells in the stroma of benign and malignant mixed tumor of the lacrimal gland.
Forty-six eyes with uveal melanoma were scanned with a computerized diagnostic ultrasound system before enucleation, and light microscope sections were obtained. Tumors were characterized by ultrasonically measured dimensions and power spectrum analysis, which provided information not available in conventional A- or B-scan ultrasonography. Histopathologic features, including cell clustering pattern, cell type, pigmentation, vascularity, and necrosis, were quantified. Statistically significant correlations were found between parameters derived from the power spectrum and histologic characteristics. Patients were followed up for up to ten years with 14 deaths occurring because of metastases. Using a Cox relative risk model with histopathologic data, a risk model comprising pigmentation and cell type (P less than .0001) was obtained. Using ultrasonic characteristics, a model comprising tumor volume and scatterer concentration (P = .0062) was obtained. The results suggest that ultrasonic tissue characterization and three-dimensional biometry may provide improved in vivo prognostic indicators for uveal melanoma.
A study relating the intralesional infiltration of lymphocytes and plasma cells to patient survival was performed on cases of uveal malignant melanoma accessed at the Armed Forces Institute of Pathology, Washington, DC (AFIP) between 1954 and 1971. The authors examined 1193 cases using light microscopy. Of the 1078 cases with technically acceptable histologic sections, 134 tumors contained 100 or more lymphocytes per 20 high-power (X400) microscopic fields (20 HPF). The prevalence was 12.4%. This was designated the "high lymphocytic" group. An equivalent number of cases with fewer lymphocytes comprised the "low lymphocytic" group. The survival rate at 15 years was 36.7% for patients in the high lymphocytic group and 69.6% for patients in the low lymphocytic group. Using the Cox model, the authors found that an increased number of lymphocytes per 20 HPF was significantly associated with decreased survival (chi-square = 21.2, P = less than 0.0001). A significant association was observed even when we controlled for other risk factors (chi-square = 6.98, P = 0.008).
We obtained maximum likelihood estimates (MLEs) of the proportion cured pi c and mean log survival time mu t for a sample of 4355 patients with intraocular melanoma whose survival times subsequent to treatment were assumed to follow a log-normal distribution. Following stratification by tumour size, MLEs of pi c and mu t derived for each stratum correlate inversely with tumour size. We then expressed pi c and mu t as continuous functions of tumour size and calculated MLEs for the parameters of these functions from the entire sample. This investigation documents for ocular melanoma a significant relationship of tumour size to both cured fraction and mean log survival time.
The authors evaluated the long-term results of iridocyclectomy to remove a lesion of the iris or ciliary body in 52 patients. The mean follow-up time was 8.5 years. The excised lesions were benign in 53% of the cases, spindle cell-type melanomas in 19% of the cases, mixed cell- or epithelioid cell-type melanomas in 25%, and an adenocarcinoma of ciliary epithelium in 2%. Visual outcome was generally good, with 43% of the patients achieving visual acuity of 6/7.5 or better and 57% achieving 6/15 or better. In 29% of the patients, enucleation was finally required, and in 10% of the patients there was metastasis of the melanoma. In 11 of the 15 patients who had a subsequent enucleation, the tumor was a melanoma of mixed cell or epithelioid cell type, and in 12 of these 15 patients the surgical margin was involved by the tumor in the iridocyclectomy specimen. All five patients with metastatic disease had melanomas of mixed cell or epithelioid cell type with involvement of the surgical margin in the iridocyclectomy specimen.
In 150 retinoblastomas the authors found a uniform thickness of the cuff of viable retinoblastoma cells that surrounds blood vessels. The mean thickness was 98.7 microns with a standard deviation of 11.9 microns. The cross-sectional area of the cuff was negatively correlated with the mitotic activity in the cuff and positively correlated with the diameter of the central vessel. The mitotic activity in the cuff of cells was inversely related to the distance from the central blood vessel. When the cuff was divided into three concentric rings, the inner ring contained a mean of 6.2 mitotic figures, the middle ring contained a mean of 2.9 mitotic figures, and the outer ring contained a mean of 0.6 mitotic figures. This pattern of growth is similar to that observed in other rapidly growing neoplasms in humans and experimental animals. In these tumors this pattern results from reduction in oxygen tension with increased distance from the central blood vessel.
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Morphometric measurements of nucleoli were done on uveal melanomas from surviving and nonsurviving patients. The melanomas were embedded in paraffin and plastic, and measurement data from Papanicolaou-stained paraffin-embedded sections, toluidine blue-stained plastic-embedded sections and scanning transmission electron micrographs (STEM) of plastic-embedded sections were compared. The results showed that one parameter, the coefficient of variation (CV) of nucleolar area, correctly classified 80% of the cases as to survival when plastic-embedded material was used and 70% of the cases when paraffin-embedded material or STEM micrographs were used. The inverse standard deviation of the nucleolar area was a better predictor of outcome than was the CV of nucleolar area only in the paraffin-embedded sections. The nucleolar measurements were most easily and rapidly performed in the plastic-embedded sections.
In a selected group of 3680 patients treated by ocular excision for uveal melanoma, 1178 deaths were attributed to this tumor during 20 years following ocular excision. Survival time was divided into intervals containing an equal number of deaths, and coefficients of the Cox statistical model were independently derived for each interval. This analysis revealed a statistically significant decline over time in the prognostic value of largest tumor dimension (LTD) and Callender cell type (CT). Mathematical considerations suggest that the prognostic value of parameters derived from other cancers may also decline with time following excision of the primary tumor.