Pathologic findings in a steroid-responsive optic nerve infarct in giant-cell arteritis.

OBJECTIVE: To investigate the pathophysiologic mechanism of optic nerve infarction in giant-cell arteritis (GCA). BACKGROUND: Previous pathologic reports of optic nerve infarction in GCA involved patients who were blind at the time of death. The optic nerve infarcts were primarily retrolaminar in localization. Simultaneous short ciliary and ophthalmic artery vasculitis was found in all patients. METHODS: Clinical neurologic and ophthalmologic examination, temporal artery biopsy, and neuroimaging tests were performed in a patient with an anterior ischemic optic neuropathy secondary to GCA. Pathologic examination of the viscera, eye, and brain were performed at autopsy 1 month later. RESULTS: A prelaminar/retrolaminar infarct was found in this patient. Subsiding vasculitis was limited to the short ciliary arteries, sparing the central retinal, pial, and ophthalmic arteries. CONCLUSIONS: The authors believe that the visual improvement observed in this patient was the result of preserved, anterior optic nerve collateral circulation, as well as the neuroprotective and anti-inflammatory effect of the corticosteroids.

Inferred natural history of uveal melanoma.

We have observed that the fatality rate of patients with posterior uveal melanomas rapidly increased from a very low rate prior to enucleation to a maximum of 8% per year during the second year after enucleation. These data suggest to us that events related to enucleation have a deleterious effect on survival, and we have postulated that these events are either the iatrogenic dissemination of tumor cells or an adverse effect on the immune-defense system, or both. Others have proposed that the relationship between enucleation and increased mortality is only happenstance. They would attribute the onset of symptoms to the rapid growth of the malignant tumor and thus claim that this brings the patient to enucleation soon after the tumor becomes malignant. We have studied 2105 cases on file in the REgistry of Ophthalmic Pathology and have found that enucleation was not always performed shortly after the onset of visual disturbance. In one third of the cases, enucleation was delayed until onset oment was not obtained until the tumor measured larger than 15 mm in diameter. Using Zelen's method to infer the natural history of uveal melanoma, we found that the mean time it took for a small tumor (less than 10 mm in diameter) to become a large tumor (greater than 15 mm) was approximately 7 years. The average age of patients treated for medium-sized tumors was 5 years less than that of patients treated for larger tumors. This is interpreted as evidence of an average delay of 5 years in the treatment of large melanomas. If this delay is taken into consideration, then the patients treated with medium-sized tumors had a worse survival during the first 7 years than did patients whose treatment was delayed until the tumor became large. After the seventh year, however, the survival was better. These findings support our hypothesis that the postoperative increase in mortality during the first several years, particularly among patients with tumors of medium size, was related to enucleation.

Retinoblastoma. The relationship of proliferating cells to blood vessels.

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.

Primary acquired melanosis of the conjunctiva.

Forty-one cases of conjunctival primary acquired melanosis (PAM) were studied to determine the frequency of progression to malignant melanoma and to establish prognostic parameters for progression to melanoma. Two subdivisions were identified: lesions with cytologically atypical melanocytes (PAM with atypia, 28 lesions, 68.3 per cent) and those lacking cytologically atypical melanocytes (PAM without atypia, 13 lesions, 31.7 per cent). None of the lesions of PAM without atypia progressed to melanoma. Thirteen of the 28 lesions of PAM with atypia (46.4 per cent) progressed to melanoma. Progression to melanoma was more frequent in the lesions of PAM with atypia if basilar hyperplasia was not the dominant histologic pattern (90 per cent progression, P = 0.02) or if any epithelioid cells were present (75 per cent progression, P = 0.02). It was not possible to determine which lesions were atypical on the basis of clinical appearance. Lesions at risk for the development of melanoma should be totally extirpated.

Malignant melanoma of the conjunctiva.

One hundred thirty-one cases of conjunctival melanoma in which biopsies had been performed were studied to determine potential factors that might affect outcome in patients with these lesions. Two groups of lesions were identified: those associated with primary acquired melanosis (melanoma with PAM, 98 cases, 74.8 per cent) and those without primary acquired melanosis (melanoma without PAM, 33 cases, 25.2 per cent). The overall mortality rate in the 131 cases was 26 per cent (34 of 131); the mortality rate due to melanoma with PAM was 25.5 per cent (25 of 98), and that due to melanoma without PAM was 27.3 per cent (9 of 33). If PAM was associated with the lesion, the presence of atypical melanocytes within the epithelium (pagetoid invasion) was a sensitive indicator of subsequent metastasis. Tumor thickness may also be useful for predicting subsequent metastases. None of the histologic parameters studied proved useful for predicting outcome in patients who had melanomas without PAM. The presence or absence of nevi had no effect on prognosis.

Alveolar soft-part sarcoma of the orbit: a clinicopathologic analysis of seventeen cases and a review of the literature.

This is a clinicopathologic study of 17 cases of alveolar soft-part sarcoma of the orbit. The mean age of patients was 23 and the median was 18 (range, 11 months to 69 years); 13 patients (76.5 per cent) were women and four were men (ratio, 3.25:1). The right and left orbits were equally involved (eight patients each), and in one the laterality was not specified. Histologically, the tumors had a distinctive organoid pattern outlined by thin-walled capillaries and were composed of nests of large polyhedral cells with abundant, finely granular, acidophilic cytoplasm. Approximately two thirds of the tumors had diagnostic PAS-positive diastase-resistant crystalline structures. Histologically, the differential diagnosis included nonchromaffin paraganglioma, granular cell tumor, metastatic renal cell carcinoma, vascular tumor, alveolar rhabdomyosarcoma, and amelanotic malignant melanoma. Electron microscopic studies of one tumor disclosed mitochondria with abnormal cristae, increased amounts of glycogen, and cytoplasmic crystalline structures with a periodicity of 8 to 10 nm. Smaller membrane-bound electron-dense granules appeared to be precursors of the crystals. Follow-up studies showed that eight patients were alive and well (median follow-up period, 11.4 years). Six of the eight patients at the time of diagnosis were 20 years of age or younger. A ninth patient was alive and well 13 years after excision of the orbital mass and four years after bilateral thoracotomy with resection of nine pulmonary nodules. Two patients died as a result of metastatic disease, one 14 years and the other 21 years after initial orbital surgery. Two patients died of other causes, one of whom had pulmonary metastases at autopsy. The follow-up period on two recent cases was less than three years, and two patients were lost to follow-up. The disease pursued an indolent clinical course. Surgery offers the best chance to control the disease.

Carcinoid tumors of the eye and orbit: a clinicopathologic study of 15 cases, with histochemical and electron microscopic observations.

This clinicopathologic study includes 15 cases of carcinoid tumors of the eye and orbit. The patients ranged in age from 14 to 86 years (median, 53). No prediction for either gender was found. Seven tumors involved the orbit, seven the choroid, and one the iris. The primary site of origin of the carcinoid tumor was known in 12 cases: seven in the bronchus, one in the trachea, and four in the ileum. In three cases an orbital tumor was present but no other known primary neoplasm was clinically apparent. The postoperative follow-up period ranged from 0 to 4 years. The urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) were elevated in four of ten patients tested, each of whom had a known primary tumor and two of whom had clinical evidence of the carcinoid syndrome. Four main histologic patterns were recognized: pattern A (solid lobules or masses), pattern B (trabecular or cord-like), pattern C (tubular or rosette-like) and pattern D (mixed). The apparently primary carcinoid tumors and the orbital or ocular metastases were closely related by their histologic patterns, histochemical staining characteristics, and ultrastructural features.

Uveal melanoma: location, size, cell type, and enucleation as risk factors in metastasis.

In this series of 3,432 cases of malignant melanoma of the choroid and ciliary body, mortality from metastasis 15 years after enucleation was 46 per cent. This mortality was at least ten times greater than has been observed with tumors of the iris, probably owing to the greater size and more malignant cytology of choroidal and ciliary body tumors. In 56 per cent of the 3,432 cases, the melanomas were composed of a mixture of spindle and epithelioid cells. The 15-year mortality of patients with melanomas of mixed cell type was three times that of patients with tumors of pure spindle cell type. In 30 per cent of the cases in this series, the melanomas of the choroid and ciliary body were larger than 15 mm in diameter. Size was highly correlated with mortality. The distribution of deaths following enucleation in the 3,432 cases was a log-normal function of time from enucleation. This indicated that metastasis occurred in these fatal cases close to the time of enucleation. The authors were also able to infer that many years were usually required for these uveal melanomas to grow from small (7 to 10 mm in diameter) to large (greater than 15 mm in diameter). These observations are consistent with the hypothesis that dissemination of tumor cells at the time of enucleation has been a major cause of metastasis with small and medium-sized uveal melanomas.

Sebaceous carcinomas of the ocular adnexa: A clinicopathologic study of 104 cases, with five-year follow-up data.

One hundred four cases of sebaceous carcinoma that arose from ocular adnexa, with at least five years' follow-up information following diagnosis, were studied to extend the authors' previous observations on various prognostic factors in these tumors. Twenty-three patients died from metastatic disease. Although sebaceous carcinomas elsewhere in the skin are rare, this study establishes that these neoplasms occur much more frequently in the ocular adnexa and have significant morphologic features that identify the more highly lethal carcinomas. The various clinicopathologic features that indicated a bad prognosis were vascular, lymphatic, and orbital invasion; involvement of both upper and lower eyelids; poor differentiation; multicentric origin; duration of symptoms greater than six months; tumor diameter exceeding 10 mm; a highly infiltrative pattern; and pagetoid invasion of the overlying epithelia of the eyelids. In many cases pagetoid change appeared to originate in the underlying sebaceous glands and from there extended to invade the overlying epithelia.

Computerized histologic assessment of malignant potential: a method for determining the prognosis of uveal melanomas.

The authors evaluated 50 cases of primary melanoma of the choroid and ciliary body. In each case, 100 cells were randomly selected from a single histologic slide, and on each cell computer-assisted measurements were made of 18 nuclear and nucleolar features. Means and standard deviations were calculated for each of these features in each tumor. Thirteen calculated variables (six means and seven standard deviations) were found to correlate significantly with patient mortality following enucleation. Standard deviations of statistically significant nuclear and nucleolar features demonstrated significantly greater correlation with mortality than the means of these features, thus confirming the great value of nuclear pleomorphism for predicting the malignant potential of uveal melanomas. Furthermore, when the standard deviation of the nucleolar circumference, a feature highly correlated with survival (P less than 0.00001), was combined with the measurement of the largest dimension of the tumor, linear discriminant analysis correctly predicted the clinical course of 88 per cent of cases.

Idiopathic solitary granuloma of the uveal tract.

We reviewed the clinical and histopathologic features of 11 cases of a distinctive solitary necrotizing granuloma of the uveal tract. No clinical or histopathologic cause for the lesion could be found in any case. The granulomas were located between the pars plana ciliaris and the equator and had an annular configuration. Uveal effusion and total retinal detachment were present in each eye. Uveitis was unilateral in all cases, and all patients were in otherwise good health. The morphologic characteristics of the solitary necrotizing granuloma suggest an infection, but the cause of this previously unreported entity remains to be determined.

Granulomatous dacryoadenitis caused by Schistosoma haematobium.

An 11-year-old boy from Sierra Leone developed a mass in the left lacrimal gland a year after trauma to the left side of the brow. Biopsy of the mass led to the diagnosis of schistosomiasis caused by Schistosoma haematobium, which had not been suspected previously. The initial occurrence in the orbit of such a rare, ectopic lesion in schistosomiasis and the possible relationship to previous trauma are features of special interest.

Primary carcinoid tumor of the orbit. A clinicopathologic study with histochemical and electron microscopic observations.

A patient with a primary carcinoid tumor of the orbit is described. No other tumor had been found during the 15-year interval since the onset of unilateral proptosis. Symptoms of the carcinoid syndrome were absent, and the urinary levels of 5-hydroxyindoleacetic acid were normal. Histologically, the bulky, noninfiltrating tumor compressed but did not invade the optic nerve. The argyrophilic cells were arranged in solid lobules and formed abundant, rosettelike structures. Pleomorphic neurosecretory granules were demonstrated by transmission electron microscopy.

The persisting pseudomelanoma problem.

We reviewed 6,169 cases in which whole eyes were submitted to the Armed Forces Institute of Pathology (AFIP), Washington, DC, between January 1970 and December 1980. We sought to determine whether there had been any change in the frequency of incorrect diagnoses of malignant melanoma since two previous studies had been conducted at the AFIP. Of 744 eyes with clear media submitted with the clinical diagnosis of malignant melanoma, the rate of incorrect diagnosis was 6.4% (48 of 744 cases). During the 11-year study, the rate of incorrect diagnoses declined from 12.5% to 1.4%. Despite that overall decrease, the locations and frequency of simulating lesions were comparable with those found in the two previous studies. We believe our current findings reflect a significant increase in diagnostic accuracy among clinicians practicing outside of major academic centers.

Malignant melanoma of the choroid in the nevus of Ota of a black patient.

To our knowledge, this report is the first description of an association of a choroidal melanoma in the nevus of Ota in a black patient. While white patients who have the nevus of Ota appear to be predisposed to the development of a malignant melanoma, this complication is rare in all nonwhite racial groups. Nevertheless, it should be realized that regardless of the patient's race, there is a greater than normal chance that a patient with the nevus of Ota might have a malignant melanoma develop within one of the affected tissues.

Nonglaucomatous cavernous degeneration of the optic nerve. Report of two cases.

The globes from two elderly women who underwent enucleation for malignant melanoma of the choroid showed cavernous degeneration of the optic nerve. Both individuals had prominent optic cups and a strong family history of severe cardiovascular disease; one patient also had mild anemia and substantial arteriosclerotic heart disease. Neither patient showed any clinical or histologic evidence of glaucoma. It is proposed that cavernous degeneration of the optic nerves in some patients may represent an aging change associated with generalized arteriosclerosis. Individuals with large optic cups may be more at risk of developing this condition.

Uveal melanoma in children and adolescents.

Five-year survival data were available in 78 cases originally classified as uveal melanomas in patients less than 20 years old. Forty-two were malignant melanomas arising from the choroid and/or ciliary body; 13 patients from this group died of metastatic disease. Factors that significantly correlated with fatality were a red, painful eye, extraocular extension at enucleation, basal tumor diameter greater than 10 mm, increased mitotic activity, and tumor necrosis. There were 36 iridic tumors; nine were reclassified as nevi. Of the 27 patients with iridic melanomas, only four died of metastases. The predominant factors relating to fatal outcome were glaucoma, extension of tumor into the ciliary body, diffuse growth, deep angle invasion, scleral invasion by tumor cells, and increased mitotic activity. Except for their relative rarity, uveal melanomas in children and adolescents did not differ significantly from their counter-parts in adults.

Prognostic factors in small malignant melanomas of choroid and ciliary body.

Two hundre seventeen small malignant melanomas, each with a volume less than 1,400/cu mm, were studied to determine what factors were useful in predicting metastasis. Using a single-factor approach with 16 risk factors, we found seven that correlated well with outcome. These were cell type, pigmentation, size (largest dimension), scleral extension, mitotic activity, location of anterior margin of the tumor, and optic nerve extension. Using a linear discriminant function, the four best factors in combination were cell type, largest dimension, scleral extension, and mitotic activity. Four variables (largest diameter, location of anterior margin, mitotic activity, and optic nerve invasion) that might be correlated with clinical observations were found to be less accurate in separating fatal and nonfatal cases than cell type alone.

Congenital glaucoma associated with a chromosomal defect. A histologic study.

A pair of eyes with congenital glaucoma, one treated by goniotomy, was examined by light and electron microscopy. Examination of the drainage angles afforded the opportunity to compare anatomic changes in the treated eye with the surgically unaltered tissue of the fellow eye. The congenital glaucoma appeared to arise from compression of the trabecular meshwork and closure of the intertrabecular and transtrabecular spaces by a discontinuous "membrane" consisting of ectopic trabecular pillars that bridged the drainage angle from the iris root to the normally positioned uveal meshwork. Cleavage of trabecular pillars during goniotomy and conversion of angle architecture to that of a nonglaucomatous neonatal eye suggest that aberrant or ectopic trabecular pillars acted mechanically in maintaining angle compression. The uveal and corneoscleral meshwork and Schlemm's canal are present and appear normal.

Diffuse iris nevus manifested by unilateral open angle glaucoma.

Uncontrolled unilateral glaucoma developed in the right eye of a 24-year-old woman. It was caused by the diffuse growth of a nonpigmented nevus of the iris into the anterior chamber angle. Histologically, the nonpigmented nevus cells in the angle were distinguishable from a proliferation of corneal endothelium. Clinically, there was no heterochromia, and a tumor was not suspected as the cause of the glaucoma.