[Giant optic disk melanocytoma complicated with massive intraocular seeding]. / Melanocitoma gigante de la papila óptica complicado con siembra intraocular masiva.

CASE REPORT: A 33 year-old female with a large, unilateral, dark tumour of the optic disk with a presumed diagnosis of melanocytoma. After a follow-up of nineteen years, the tumour produced massive intraocular seeding with cataract, secondary glaucoma (pigmentary, melanocytomalytic, inflammatory and pupillary seclusion glaucoma) and amaurosis. The eye is enucleated and the pathological examination confirmed the diagnosis. DISCUSSION: Optic disk melanocytoma is a benign stationary tumour. However, sometimes that are to complications, including visual loss. Our case confirms that vitreous seeding is due to tumour necrosis with dissemination of tumoral debris and melanin, which are phagocytized by macrophages and produce an inflammatory reaction, trabecular plugging and ocular hypertension.

Melanocitoma gigante de la papila óptica complicado con siembra intraocular masiva / Giant optic disk melanocytoma complicated with massive intraocular seeding

Caso clínico:Mujer de 33 años con gran tumoración oscura sobre papila óptica unilateral diagnosticadapresuntamente comomelanocitoma. Tras seguimiento de 19 años, la tumoraciónproduce siembra intraocular masiva con catarata, glaucoma secundario (pigmentario, melanocitomalítico,inflamatorio y seclusión pupilar) y amaurosis. Tras enucleación se confirmaanatomopatológicamente el diagnóstico.Discusión: El melanocitoma de papila óptica es un tumor benigno estacionario, pero rarasveces ocasiona complicaciones, incluida la pérdida visual. Nuestro caso corrobora que lasiembra vítrea está causada por necrosis tumoral con diseminación de detritus tumoralesy melanina, que fagocitados por macrófagos, producen reacción inflamatoria, ocupacióntrabecular e hipertensión ocular(AU)

Case report: A 33 year-old female with a large, unilateral, dark tumour of the optic diskwith a presumed diagnosis of melanocytoma. After a follow-up of nineteen years, thetumour produced massive intraocular seeding with cataract, secondary glaucoma (pigmentary,melanocytomalytic, inflammatory and pupillary seclusion glaucoma) and amaurosis.The eye is enucleated and the pathological examination confirmed the diagnosis.Discussion: Optic disk melanocytoma is a benign stationary tumour. However, sometimesthat are to complications, including visual loss. Our case confirms that vitreous seedingis due to tumour necrosis with dissemination of tumoral debris and melanin, which arephagocytized by macrophages and produce an inflammatory reaction, trabecular pluggingand ocular hypertension(AU)

Detection of varicella zoster virus DNA in some patients with giant cell arteritis.

PURPOSE: The purpose of this study was to determine whether an association exists between giant cell arteritis (GCA) and the presence of varicella-zoster virus (VZV), by using histologic, molecular, immunohistochemical, and ultrastructural analyses of temporal artery biopsy specimens. METHODS: In a randomized masked study, 64 temporal artery biopsy specimens were analyzed by PCR for VZV DNA. The samples included 35 specimens histologically positive and 29 specimens histologically negative for GCA. Immunohistochemical staining for VZV viral antigen IE-63 was performed on seven of the specimens positive for GCA and five negative specimens. Transmission electron microscopy (TEM) was performed on five of the specimens positive for GCA. RESULTS: PCR was positive for VZV DNA in 9 (26%) temporal arteries tested that showed histologic evidence of GCA. The remaining 26 histologically positive temporal arteries and all 29 histologically negative arteries tested gave negative PCR results for VZV DNA. Statistical analysis (z-test) comparing the association of VZV DNA between the specimens that were positive and negative for GCA showed a significant difference (P = 0.010). Immunohistochemical studies were positive in several biopsy specimens within adventitial histiocytes-macrophages, but these results did not correlate with either the presence or absence of VZV DNA or with the histologic evidence of GCA. No viral particles were observed by TEM. CONCLUSIONS: This study showed a significant association of VZV DNA to temporal artery biopsy samples positive for GCA compared with the negative specimens. The results support the hypothesis that VZV may play a role in the pathogenesis of some cases of GCA. However, PCR, immunohistochemical, and electron microscopic findings suggest the virus is present at extremely low quantities, is abortively replicating, or is latent.

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.

Corneal microsporidiosis. Report of case, including electron microscopic observations.

OBJECTIVE: To report a case of corneal stromal infection caused by a protozoon of the genus MICROSPORIDIA:, including clinical, histopathologic, and electron microscopic observations. DESIGN: Case report. METHODS: Light and electron microscopy studies were performed on keratectomy specimens from a 67-year-old immunocompetent man who had a unilateral chronic stromal keratitis that was refractory to medical treatment. Initial corneal biopsy followed by lamellar and penetrating keratoplasty were performed on the patient. All the specimens were studied histopathologically. RESULTS: Light microscopy of the corneal biopsy and the subsequent keratectomy specimens demonstrated myriad small, round to oval microsporidial organisms measuring 3.5 to 5.0 micrometer in length that stained positively with the periodic acid-Schiff, Grocott-methenamine silver, and acid-fast methods and were gram positive. Electron microscopic observations demonstrated viable blastospores that had a thin osmiophilic outer cell wall and contained 11 to 13 coils of the filament. The light and electron microscopic features, the tinctorial characteristics, and the selective corneal stromal involvement are consistent with microsporidial keratitis. CONCLUSIONS: Microsporidiosis should be considered in the differential diagnosis of a culture-negative stromal keratitis refractory to medical treatment. The diagnosis can be easily established based on the morphologic features of the protozoa in the keratectomy specimens. No effective medical treatment for the stromal disease is available. Full-thickness keratoplasty is suggested because, in our patient, lamellar keratoplasty did not preclude recurrence of the disease.

Melanocytoma of the ciliary body diagnosed by fine-needle aspiration biopsy.

A 55-yr-old African American man was referred for evaluation of a mass involving the anterior choroid/ciliary body in his left eye. Dilated fundus examination revealed a large, deeply pigmented mass associated with an exudative retinal detachment. Ultrasonography demonstrated an elevated mass which involved the anterior uvea and showed low reflectivity by standardized A-scan. Cytologic examination of fine needle aspiration (FNA) biopsy from the tumor was interpreted as a melanocytoma. The patient developed a total retinal detachment and secondary glaucoma which led to enucleation of the eye. Histopathologic examination confirmed the diagnosis of melanocytoma. To our knowledge, this is the first report in which the diagnosis of uveal melanocytoma was established by FNA biopsy and later confirmed histopathologically.

Melanocytoma (magnocellular nevus) of the ciliary body: report of 10 cases and review of the literature.

PURPOSE: To describe the characteristics of melanocytoma (magnocellular nevus) of the ciliary body, an unusual melanocytic tumor. DESIGN: Retrospective, clinicopathologic case series. METHODS: Ten melanocytomas of the ciliary body were examined histopathologically. Five tumors were also examined by transmission electron microscopy. The clinical histories were abstracted from the patients' medical records. We compared the clinical, histopathologic, and ultrastructural findings of our 10 cases with those previously reported in the literature. MAIN OUTCOME MEASURES: To define clinical and histopathologic parameters of this rare tumor. RESULTS: A total of 40 cases were summarized, including our 10 and 30 previously reported cases. The mean age of the 40 cases was 47 years. Twenty-six patients were female (65%), fourteen were male (35%). No laterality was observed. Eighty percent of the patients were white and 10% were black. The most common clinical presentation was an asymptomatic dark spot involving the iris and ciliary body or the sclera. Involvement of chamber angle structures, with or without intrascleral extension, was observed in 85% (34 of 40 patients); but only 12% (2 of the 17 patients for whom information about intraocular pressure and local extension was available) had elevated preoperative intraocular pressure. By electron microscopy, two distinct cell types were observed. CONCLUSIONS: Melanocytomas can usually be distinguished from other pigmented lesions of the ciliary body by histopathologic criteria, but may be difficult to differentiate before surgery from other pigmented ciliary body tumors, including malignant melanomas, adenomas, and adenocarcinomas of the pigmented ciliary epithelium. Most tumors can be managed conservatively by iridocyclectomy.

Epithelioid hemangioma of the orbit.

OBJECTIVE: To describe the histopathologic features of two cases of epithelioid hemangioma occurring in the orbit and to distinguish this condition from Kimura's disease and from other vascular lesions of proliferated endothelium. DESIGN: Two interventional case reports. INTERVENTION: Treatment consisted of orbitotomy with excision of the tumor. MAIN OUTCOME MEASURES: Histopathologic examination including light microscopy, immunohistochemistry, and electron microscopy and clinical follow-up. RESULTS: In one case, there was no local recurrence after 2 years of follow-up. In the other case, local recurrence required re-excision 2 years after surgery with no apparent recurrence 16 years later. Histopathologic examination of both tumors disclosed an epithelioid hemangioma. A characteristic finding was the presence of peculiar plump vacuolated endothelial cells lining the vascular lumina. CONCLUSIONS: Epithelioid hemangioma is an uncommon benign vascular tumor that can occur in the orbit, and surgical excision is usually required. It is the same condition as angiolymphoid hyperplasia with eosinophilia. There are distinct clinical and histopathologic characteristics to distinguish epithelioid hemangioma from Kimura's disease and from other vascular tumors.

T-cell lymphoproliferative disorder of vitreous associated with mycosis fungoides.

59-year-old man with a history of mycosis fungoides developed loss of visual acuity and visual field in the left eye. Epiretinal lesions were present in the right eye and multifocal choroidal lesions, optic disc edema, and vitritis were present in the left eye. A diagnostic vitrectomy was performed and cytologic examination of the vitreous confirmed the diagnosis of T-cell lymphoproliferative disorder. Systemic and intrathecal chemotherapy resulted in marked improvement in ocular signs and symptoms. At last follow-up, the patient was found to have improved visual acuity in the left eye; however, significant worsening of his systemic condition developed and he died shortly thereafter.

Use of agar in ophthalmic pathology: a technique to improve the handling and diagnosis of temporal artery biopsies, subfoveal membranes, lens capsules, and other ocular tissues.

DESIGN: Prospective laboratory methodology study. PURPOSE: Certain tissues, by virtue of their shape and extreme thinness or pliability, are difficult to position correctly during routine paraffin embedding to provide the optimal orientation for histopathologic studies. Biopsy specimens from temporal arteries must be sampled at different points along the length of the artery. Other tissues such as subfoveal neovascular membranes and fragments of lens capsule lack the thickness and rigidity to be positioned on edge to yield cross-sectional views. The authors' technique improves the orientation and thereby maximizes the histologic information obtained from such specimens. METHODS AND MATERIALS: From January 1, 1990, to April 30, 1999, the authors studied 500 consecutive temporal artery biopsy specimens and 200 successive subfoveal neovascular membranes. RESULTS: Cutting a 20-mm cylindrical fragment of temporal artery at 1- to 1.5-mm intervals yielded approximately 13 to 20 cross-sections along the length of the artery. When the specimens were positioned together and embedded in agar, the pathologist could easily study multiple cross-sections of the artery. Additionally, using the agar technique, the authors were able to obtain cross-sections of other specimens submitted, such as subfoveal neovascular membranes, and studied each of the different layers to evaluate the disease process. By the same method, the authors placed small fragments of lens capsule with underlying cortex on edge and readily identified short, gram-positive coccobacilli consistent with Propionibacterium acnes endophthalmitis. CONCLUSION: The agar technique can greatly improve the quality of diagnostic information gleaned from temporal artery biopsy specimens and other small tissue samples.

Posterior polymorphous dystrophy associated with posterior amyloid degeneration of the cornea.

PURPOSE: To describe a case of posterior polymorphous dystrophy associated with posterior amyloid degeneration of the cornea confirmed histopathologically and immunohistochemically. METHODS: An 80-year-old woman with corneal opacities required penetrating keratoplasty. The keratectomy specimen was evaluated by light microscopy and immunohistochemistry. RESULTS: Microscopic examination of the keratectomy specimen showed scattered fusiform deposits located in the deep corneal stroma. Congo red stains of the fusiform deposits confirmed the diagnosis of amyloidosis. Immunohistochemical stains for cytokeratin (AE1/AE3) showed that the endothelial cells were immunoreactive, confirming the diagnosis of posterior polymorphous dystrophy. CONCLUSIONS: To our knowledge, the association between posterior polymorphous dystrophy and posterior amyloid degeneration has not been reported previously.

Immunohistochemical localization of ganciclovir in the human retina.

PURPOSE: To localize ganciclovir in the retina of human eyes treated with intravenous or intravitreal ganciclovir for cytomegalovirus (CMV) retinitis. METHODS: Paraffin-embedded five-micron sections of autopsy eyes were obtained from seven patients as follows: two patients with CMV retinitis treated with intravenous ganciclovir; two patients with CMV retinitis treated with an intravitreal sustained-release ganciclovir device; one patient with CMV retinitis treated with intravenous foscarnet; and two patients with AIDS without CMV retinitis who did not receive any anti-CMV therapy. The paraffin was removed from the sections, and indirect immunofluorescent staining was performed, using an antiserum to ganciclovir. RESULTS: Bright fluorescent staining was noted in the retinal pigment epithelium (RPE) and photoreceptor outer segments of eyes treated with intravenous or intravitreal ganciclovir, but not in eyes treated with foscarnet or without CMV retinitis. In addition, patches of bright fluorescent staining of the internal limiting membrane was noted in eyes treated with intravitreal ganciclovir. CONCLUSIONS: Ganciclovir is detected in the outer retina of patients with CMV retinitis treated with intravenous or intravitreal therapy. The drug is detected also in the internal limiting membrane in eyes treated with the intravitreal sustained-release ganciclovir device.

Hepatocellular carcinoma metastatic to the orbit.

We report a rare case of orbital metastasis from hepatocellular carcinoma and review previously documented cases of this condition. The clinical, histopathological, and immunohistochemical characteristics of hepatocellular carcinoma metastatic to the orbit are described. Results from histopathological examination and histochemical findings of the orbital mass established the diagnosis. A review of 10 cases of metastatic hepatocellular carcinoma to the eye and orbit disclosed painful proptosis as the most common clinical sign of hepatocellular carcinoma metastatic to the orbit. In 5 (56%) of the 9 cases that had orbital metastasis (including the present case), the diagnosis was made after the patient first was examined with symptoms from the orbital mass. Metastatic hepatocellular carcinoma should be considered as a rare cause of painful proptosis. While patients usually are seen with signs and symptoms of widespread metastatic carcinoma, patients with hepatocellular carcinoma with orbital involvement may be first examined by the ophthalmologist because of the clinical manifestations of the disease, proptosis and pain. Other orbital lesions associated with painful proptosis are discussed briefly.

Orbital pathology associated with diabetes mellitus.

Diabetes mellitus may be associated with or result in diverse orbital and adnexal problems. It may include mild manifestations, such as blepharoptosis, blepharitis, xanthomas, increased tear-film glucose levels, and calcification of the trochlear apparatus. More severe findings involve third, fourth, and sixth cranial neuropathies. Finally, the physician always should be alert for the possibility of orbital infections in the diabetic population, especially the life-threatening rhinocerebral mucormycosis.

Malignant epithelial tumors of the lacrimal gland: a clinicopathologic study of 21 cases.

OBJECTIVE: To analyze 120 lacrimal gland masses collected during a 23-year period in the Ophthalmic Pathology Laboratory at the Cullen Eye Institute, Houston, Tex. METHODS: Of the 120 lacrimal gland tumors, we focused on a detailed clinicopathologic study of 21 malignant epithelial tumors. Follow-up was available in 19 (90%) of 21 cases. RESULTS: About two thirds of the masses (75 cases) were inflammatory, one third (41 cases) were of epithelial origin, and 3% (4 cases) were malignant lymphomas. Of the epithelial tumors, 17 (41%) were benign mixed tumors, 12 (29%) were adenoid cystic carcinomas arising de novo, 2 (5%) were adenocarcinoma arising de novo, 7 (17%) were malignant mixed tumors, and 3 (7%) were metastatic carcinoma. All of the patients with adenoid cystic carcinoma had local recurrences, and 60% of the patients died of their tumors (mean survival, 5 years); only 2 patients were alive 13 and 16 years after the initial surgery, both of whom had radical surgical procedures for recurrence following orbital exenteration. CONCLUSION: The histopathologic classification and management of these tumors are discussed. This study supports the dismal prognosis of adenoid cystic carcinoma arising de novo.

Malignant nonteratoid medulloepithelioma of the ciliary body in an adult.

BACKGROUND: The authors describe a 62-year-old man with a malignant nonteratoid malignant medulloepithelioma of the ciliary body with extension into the anterior choroid and posterior chamber. He developed gradual loss of vision in his right eye, and a clinical diagnosis of malignant melanoma of the ciliary body and choroid was made. RESULTS: Histopathologic examination of the enucleated eye showed a malignant nonteratoid medulloepithelioma of the ciliary body with extension into the anterior choroid and posterior chamber. CONCLUSION: This report provides clinicopathologic evidence that intraocular medulloepithelioma can occur rarely in an adult. The lesion clinically may mimic a malignant melanoma. The authors also summarize five previously reported cases of this unusual lesion.

Conjunctival amelanotic malignant melanoma arising in primary acquired melanosis sine pigmento.

BACKGROUND: The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. METHODS: Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. STUDY DESIGN: Case report. RESULTS: Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. CONCLUSIONS: Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.

Melanogenic neuroectodermal tumor of the retina (primary malignant melanoma of the retina).

A 35-month-old girl with leukocoria was clinically diagnosed with unilateral sporadic retinoblastoma. Macroscopic examination of her enucleated eye disclosed a white retinal tumor that appeared to be a retinoblastoma. Histopathologic examination, however, revealed that the tumor was composed of poorly differentiated neuroblastic cells, larger spindle-shaped cells, and anaplastic epithelioid cells, which is inconsistent with retinoblastoma. Immunohistochemical testing disclosed that the tumor cells were immunoreactive for melanoma-specific antigen HMB-45, while electron microscopy showed premelanosomes in the tumor cells, both of which are consistent with melanogenesis. To our knowledge, such an ocular tumor has not been reported previously.