A case report of a primary apocrine adenocarcinoma of the eyelid with literature review.

INTRODUCTION: Primary Apocrine adenocarcinomas (PAA) are very infrequent tumors that are often confused initially with benign lesions. Little is known about this disease and there is still much to be clarified. We present a case of PAA on the eyelid successfully treated with surgery alone and a literature review regarding what is currently described about this disease. METHODS: Noncomparative, retrospective case report of a patient with PAA on the eyelid succesfully treated with surgery alone and a literautre review. RESULTS: A 91-year-old man with a 2 months lesion on the upper left eyelid was treated with surgery alone with oncological margins of 5mm. The Hystopathology diagnosis was a PAA of the eyelid and free margins were obtained. After 12 months of follow-up, the patient does not show any signs of local recurrence or distant metastasis. A review of the literature suggests these tumors are located more frequently in the axilla (50%) and secondly in the head and neck (35%), with similar distribution in the upper (41%) and lower eyelid (45%). The most commonly used treatment is surgical excision, but radiotherapy and chemotherapy have also been used with variable results. CONCLUSIONS: PAA is a very rare and aggressive tumor. Because it is so infrequent, treatments are based on the sporadic cases encountered in the literature. As more cases are reported, more can be elucidated about the characteristics of this tumor, its behavior and best treatment choice and this may allow progress in the understanding and management of this disease.

Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study.

PURPOSE: Intravitreal melphalan is emerging as an effective treatment for refractory vitreous seeds in retinoblastoma, but there is limited understanding regarding its toxicity. This study evaluates the retinal and systemic toxicity of intravitreal melphalan in retinoblastoma patients, with preclinical validation in a rabbit model. DESIGN: Clinical and preclinical, prospective, cohort study. PARTICIPANTS: In the clinical study, 16 patient eyes received 107 intravitreal injections of 30 µg melphalan given weekly, a median of 6.5 times (range, 5-8). In the animal study, 12 New Zealand/Dutch Belt pigmented rabbits were given 3 weekly injections of 15 µg of intravitreal melphalan or vehicle to the right eye. METHODS: Electroretinogram (ERG) responses were recorded in both humans and rabbits. For the clinical study, ERG responses were recorded at baseline, immediately before each injection, and at each follow-up visit; 82 of these studies were deemed evaluable. Median follow-up time was 5.2 months (range, 1-11). Complete blood counts (CBCs) were obtained on the day of injection at 46 patient visits. In the animal study, ERG responses were obtained along with fluorescein angiography, CBCs, and melphalan plasma concentration. After humane killing, the histopathology of the eyes was evaluated. MAIN OUTCOME MEASURES: For the clinical study, we measured peak-to-peak ERG amplitudes in response to 30-Hz photopic flicker stimulation with comparisons between ERG studies before and after intravitreal melphalan. For the animal study, we collected ERG parameters before and after intravitreal melphalan injections with histopathologic findings. RESULTS: By linear regression analysis, over the course of weekly intravitreal injections in retinoblastoma patients, for every additional injection, the ERG amplitude decreased by approximately 5.8 µV. The ERG remained stable once the treatment course was completed. In retinoblastoma patients, there were no grade 3 or 4 hematologic events. One week after the second injection in rabbits, the a- and b-wave amplitude declined significantly in the melphalan treated eyes compared with vehicle-treated eyes (P<0.05). Histopathology revealed severely atrophic retina. CONCLUSIONS: Weekly injections of 30 µg of melphalan can result in a decreased ERG response, which is indicative of retinal toxicity. These findings are confirmed at an equivalent dose in rabbit eyes by ERG measurements and by histopathologic evidence of severe retinal damage. Systemic toxicity with intravitreal melphalan at these doses in humans or rabbits was not detected.

Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma.

Treatment of intraocular retinoblastoma with vitreous seeding is a challenge. Different routes of chemotherapy administration have been explored in order to attaining pharmacological concentrations into the posterior chamber. Intravitreal drug injection is a promissing route for maximum bioavailability to the vitreous but it requires a well defined dose for achieving tumor control while limited toxicity to the retina. Topotecan proved to be a promising agent for retinoblastoma treatment due to its pharmacological activity and limited toxicity. High and prolonged concentrations were achieved in the rabbit vitreous after 5 µg of intravitreal topotecan. However, whether a lower dose could achieve potentially therapeutic levels remained to be determined. Thus, we here study the pharmacokinetics of topotecan after 0.5 µg and the toxicity profile of intravitreal topotecan in the rabbit eye as a potential treatment of retinoblastoma. A cohort of rabbits was used to study topotecan disposition in the vitreous after a single dose of 0.5 µg of intravitreal topotecan. In addition, an independent cohort of non-tumor bearing rabbits was employed to evaluate the clinical and retinal toxicity after four weekly injections of two different doses of intravitreal topotecan (Group A, 5 µg/dose; Group B, 0.5 µg/dose) to the right eye of each animal. The same volume (0.1 ml) of normal saline was administered to the left eye as control. A third group of rabbits (Group C) served as double control (both eyes injected with normal saline). Animals were weekly evaluated for clinical and hematologic values and ocular evaluations were performed with an inverse ophthalmoscope to establish potential topotecan toxicity. Weekly controls included topotecan quantitation in plasma of all rabbits. Electroretinograms (ERGs) were recorded before and after topotecan doses. One week after the last injection, topotecan concentrations were measured in vitreous of all eyes and samples for retinal histology were obtained. Our results indicate that topotecan shows non linear pharmacokinetics after a single intravitreal dose in the range of 0.5-5 µg in the rabbit. Vitreous concentration of lactone topotecan was close to the concentration assumed to be therapeutically active after 5 h of 0.5 µg intravitreal administration. Eyes injected with four weekly doses of topotecan (0.5 or 5 µg/dose) showed no significant differences in their ERG wave amplitudes and implicit times in comparison with control (p > 0.05). Animals showed no weight, hair loss or significant changes in hematologic values during the study period. There were no significant histologic damage of the retinas exposed to topotecan treatments. After intravitreal administration no topotecan could be detected in plasma during the follow-up period nor in the vitreous of treated and control animals after 1 week of the last injection. The present data shows that four weekly intravitreal injection of 5 µg of topotecan is safe for the rabbit eye. Despite multiple injections of 0.5 µg of topotecan are also safe to the rabbit eye, lactone topotecan vitreous concentrations were potentially active only after 5 h of the administration. We postulate promising translation to clinics for retinoblastoma treatment.

Primary undifferentiated large cell carcinoma of the lacrimal gland.

PURPOSE: To report a unique case of primary undifferentiated large cell carcinoma (LCCA) of the lacrimal gland, a tumor not previously described in the ophthalmic literature. DESIGN: Single interventional case report. PARTICIPANTS: A patient affected by undifferentiated LCCA of the lacrimal gland. METHODS: A 65-year-old white man with a 3-month history of a painful mass in the left lacrimal gland fossa underwent an incisional biopsy that revealed a "high-grade" epithelial malignancy. Systemic workup revealed enlargement of the regional lymph nodes, and subsequently the patient underwent extended exenteration with clear histologic margins and radical neck lymphadenectomy followed by adjunctive radiotherapy. Fifteen months postoperatively, the patient is alive and well without evidence of local recurrence or metastatic disease. MAIN OUTCOME MEASURES: Treatment result, evidence of local recurrences or distant metastasis, and follow-up. RESULTS: Histologic examination revealed a poorly circumscribed tumor composed of large cells invading orbital fat, lateral rectus muscle, and peripheral nerves. The surrounding orbital bone was infiltrated, but the surgical margins were clear. The cell population was composed of large cells (>30 µm) with eosinophilic cytoplasm and ovoid and irregular nuclei containing a prominent nucleoli and coarse chromatin. The cell borders were well defined. Mitosis figures were abundant, and Ki-67 was positive in more than 60% of the cells. The cells were arranged in cords and trabeculae or irregular sheets of discohesive cells. The immunophenotype analysis showed positivity for cytokeratin but negative cytokeratin 20 stains, which is considered a distinctive feature of LCCA. CONCLUSIONS: Undifferentiated LCCAs are rare tumors of the major salivary glands, especially the parotid gland. Primary undifferentiated LCCA of the lacrimal gland has never been reported in the literature. Differential diagnosis must include a primary source in another organ. Given the aggressive nature of the tumor, radical surgery followed by radiotherapy is recommended, but evidence-based indications regarding the preferred line of treatment are lacking and the prognosis remains guarded. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Early histologic and functional study of radial optic neurotomy outcomes in normal rat eyes.

BACKGROUND: Radial optic neurotomy (RON) has been proposed as a treatment for central retinal vein occlusion. However, it is still under debate whether RON would be an adequate treatment or a dangerous procedure, and persuasive animal studies are lacking. The aim of this study was to analyze the early histologic and functional outcomes of RON in normal rat eyes. METHODS: Radial optic neurotomy was performed by cutting into the optic nerve edge at the nasal hemisphere, while the contralateral eye underwent a sham procedure. The retinal function was assessed by scotopic electroretinography, and the visual pathway was assessed by flash visual evoked potentials. Intraocular pressure was assessed with a tonometer, the pupillary light reflex was measured after exposing eyes to a 30-second light flash, whereas the optic nerve head structure was examined by histologic analysis. RESULTS: In normal rat eyes, RON provoked minor histologic alterations at the optic nerve head level and a transient decrease in the electroretinography. No changes in visual evoked potentials, intraocular pressure, and pupillary light reflex were observed in rat eyes submitted to RON. CONCLUSION: To our knowledge, this is the first study describing the early histopathologic and functional consequences of RON in normal rat eyes.

Sequential in vivo confocal microscopy study of corneal wound healing after cross-linking in patients with keratoconus.

PURPOSE: To evaluate the short- and long-term sequential histological changes of the cornea in vivo after corneal collagen cross-linking (CXL) in patients with keratoconus. METHODS: Eighteen patients with keratoconus (Amsler-Krumeich classification: stages I, II, and III) underwent CXL with riboflavin/ultraviolet A (UVA) in one eye. The corneas were examined preoperatively and within 5 hours, 7 and 14 days, and 1, 3, 6, 9, 12, 18, 24, and 36 months after the procedure using in vivo confocal microscopy. RESULTS: Early changes included edema, superficial nerve loss, cellular modifications, and isolated endothelial damage. At intermediate time points, there was nerve fiber regeneration, increased reflectivity of the extracellular matrix, enlarged keratocytes and extracellular deposits, and remodeling of the endothelial layer (two eyes). At later time points, loss of keratocytes and remodeling of the extracellular deposits were noted. CONCLUSIONS: Although the cornea has no significant tissue modifications clinically after CXL, this study has shown that corneal wounding by riboflavin/UVA collagen CXL induces cellular wound-healing mechanisms and alters the normal structure and cellularity of the cornea for up to 36 months.

One-year follow-up of epithelial corneal cell sheet allografts mounted on platelet poor plasma in rabbits.

PURPOSE: To evaluate the usefulness of epithelial corneal sheets mounted on platelet poor plasma (PPP) for allograft transplantation of rabbits with total limbal stem cell deficiency (LSCD) and to prove its efficacy at 1 year after surgery. METHODS: LSCD was induced in 21 female rabbits by mechanical keratectomy. To configure the grafts, limbal biopsies were taken from male rabbits and cells were cultured on a fibroblast feeder layer grown on clotted autologous PPP. After keratectomy, grafts were sutured over the stroma. Control groups consisted of no implant or an implant of clotted PPP. Rabbits were euthanized at 3 and 12 months. Corneas and cultured sheets were processed for histopathology and immunohistochemistry (K3/12 and K19). Gender analysis was performed at 4 and 7 months. RESULTS: One rabbit had endophthalmitis, and another died of no apparent cause. The rest of the animals treated had no inflammation, showed a stratified epithelium, keratin 3/12 expression, and no expression of keratin 19. At 1 year, seven of eight rabbits showed no LSCD or corneal rejection signs. Y chromosomes were detected at 4 and 7 months postoperatively. All controls showed LSCD signs, erratic epithelium, and minimal cell differentiation; they revealed a slight expression of K3/12 and an expression of K19 in patchy patterns. CONCLUSIONS: Allografts contributed to restoring a healthy eye surface without signs of graft rejection. This technique seems to be a promising procedure for bilateral ocular surface diseases and may be useful for new therapeutic strategies.

Visual loss secondary to orbital apex invasion as the first manifestation of recurrent nasopharyngeal carcinoma.

A 51-year-old white man was referred for evaluation of visual loss in the right eye caused by an apical orbital lesion. His medical history was positive for "lymphoepithelial carcinoma" of the nasopharynx successfully treated with radiotherapy 6 years previously. Cranial CT showed a diffuse orbital mass extending from the pterygopalatine fossa, infiltrating the inferior orbital fissure, the orbital apex, and the cranial cavity. Results from an incisional biopsy of the lesion were consistent with the diagnosis of nasopharyngeal carcinoma, nonkeratinizing lymphoepithelial variant of squamous cell carcinoma. The patient underwent stereotactic radiosurgery, which arrested the tumor progression. Orbitocranial recurrence of nasopharyngeal carcinoma is rare and ocular symptoms may be the first manifestation of the disease.

Epithelial tumors of the lacrimal gland: an update.

PURPOSE OF REVIEW: The goal of this article is to offer an update on the treatment and prognosis of the most common epithelial tumors of the lacrimal gland, report on new pathological entities and offer a review of the classification of lacrimal gland tumors. RECENT FINDINGS: Improvements have been made in the understanding of lacrimal gland lesions with the knowledge that lacrimal gland tumors compare to the more common counterparts of the major salivary glands. Therefore, the WHO's classification of salivary gland tumors has been adapted to the lacrimal gland pathology. Until recently, primary adenocarcinomas of the lacrimal gland were not further subclassified, but they can now be divided into low-grade and high-grade malignancies. The adjunctive use of intra-arterial cytoreductive chemotherapy for the management of adenoid cystic carcinoma is one of the most important advancements on the management of these aggressive tumors. Another important step forward has been taken on carcinoma ex pleomorphic adenoma of the lacrimal gland, which is subclassified into noninvasive carcinoma, with an excellent prognosis after complete excision and invasive carcinoma for which the prognosis is still guarded despite adjunctive radiotherapy. SUMMARY: This article offers an update on diagnosis, classification and treatment of common and rare epithelial lacrimal gland tumors.

Involvement of purinergic P2 receptors in experimental retinal neovascularization.

PURPOSE: The present study was aimed to investigate the expression of purinergic P2 receptors in oxygen-induced retinal neovascularization. METHODS: Immunohistochemistry was used to study the expression of purinergic P2Y2 and P2X2 receptors in the neonatal mouse retina during normal vascular development and after oxygen-induced retinopathy (OIR). The effect of the P2 antagonists, suramin and PPADS, on the extent of oxygen-induced retinal neovascularization was analyzed. RESULTS: In normal mice, the expression of P2Y2 receptors was weak throughout the retina, whereas P2X2 receptor expression was detected in the outer plexiform layer. In mice treated with oxygen, P2Y2 expression was detected in the ganglion and in the nerve fiber layers, whereas P2X2 expression was found in the inner and outer plexiform layers. Oxygen-induced preretinal neovascularization was strongly inhibited by the P2 antagonists, suramin (p<0.05) and PPADS (p<0.05), and this was accompanied by a down-regulation of P2X2 receptor expression in the inner plexiform layer in suramin-treated mice. CONCLUSIONS: The data suggest that purinergic P2 receptors are involved in neovascularization associated with OIR.

Corneal Neovascularization: A Combined Approach of Bevacizumab and Suramin Showed Increased Antiangiogenic Effect Through Downregulation of BFGF and P2X2.

PURPOSE: The objective is to analyze the antiangiogenic mechanism of suramab, a pharmaceutical compound of bevacizumab and suramin, in a rabbit model of corneal angiogenesis. MATERIAL AND METHODS: Corneal neovascularization was induced in four groups of six New Zealand White rabbits by applying a filter paper disk soaked in 1 M Na (OH) on the central cornea. Group one was treated after injury with intravenous suramab at a dose equivalent to 3 mg/kg of bevacizumab and 10 mg/kg of suramin. Group two was treated with intravenous bevacizumab (5 mg/kg). Group three was treated with 10 mg/kg of suramin while the control group received no treatment. Digital photographs were taken at days 9, 15, 21, and 35. Neovessel formation was quantified giving a 0-4 score to each quadrant according to the centripetal growth of the longest vessel (neovessel index, NVI). Animals were sacrificed at day 35. Corneas were processed for histology, immunohistochemistry, and Western-blot using primary antibodies against P2X2, basic fibroblast growth factor (bFGF), LYVE-1, PECAM-1, and vascular endothelial growth factor-A (VEGF-A). RESULTS: Suramab significantly reduced neovessel growth (mean NVI: 4.2) compared to bevacizumab (8.4), suramin (7.22), and control animals (12.2) at 35 days post-injury (p < 0.01). A lower protein expression of P2X2, bFGF, LYVE-1, PECAM-1, and VEGF-A was found in the cornea of suramab animals than in the other groups of animals. CONCLUSIONS: Joint downregulation of bFGF, P2X2, bFGF, and LYVE-1 constitutes a mechanism that induces greater and longer inhibition of corneal angiogenesis. Results might be relevant to ophthalmic care. Ocular administration of suramab is currently being investigated.

Possible neuroprotective role of P2X2 in the retina of diabetic rats.

BACKGROUND: Purinergic receptors are expressed in different tissues including the retina. These receptors are involved in processes like cell growth, proliferation, activation and survival. ATP is the major activator of P2 receptors. In diabetes, there is a constant ATP production and this rise of ATP leads to a persistent activation of purinergic receptors. Antagonists of these receptors are used to evaluate their inhibition effects. Recently, the P2X2 has been reported to have a neuroprotective role. METHODS: We carried out a study in groups of diabetic and non-diabetic rats (N = 5) treated with intraperitoneal injections of PPADS, at 9 and 24 weeks of diabetes. Control group received only the buffer. Animals were euthanized at 34 weeks of diabetes or at a matching age. Rat retinas were analyzed with immunohistochemistry and western blot using antibodies against GFAP, P2X2, P2Y2 and VEGF-A. RESULTS: Diabetic animals treated with PPADS disclosed a much more extended staining of VEGF-A than diabetics without treatment. A lower protein expression of VEGF-A was found at the retina of diabetic animals without treatment of purinergic antagonists compared to diabetics with the antagonist treatment. Inhibition of P2X2 receptor by PPADS decreases cell death in the diabetic rat retina. CONCLUSION: Results might be useful for better understanding the pathophysiology of diabetic retinopathy.

Treatment of Nonmetastatic Unilateral Retinoblastoma in Children.

Importance: Multi-institutional collaborative studies that include large patient populations for the management of retinoblastoma with histopathological risk factors could provide important information for patient management. Objective: To evaluate the implementation of a strategy for the management of nonmetastatic unilateral retinoblastoma in children based on standardized diagnostic and treatment criteria. Design, Setting, and Participants: This single-arm prospective study applied a strategy based on a single-center experience. The setting was a multicenter study in Latin America (Grupo de America Latina de Oncologia Pediatrica [GALOP]). Participants were children with nonmetastatic unilateral retinoblastoma (staged with the International Retinoblastoma Staging System). The study opened on July 1, 2008, and closed on December 31, 2014. Follow-up was updated until June 30, 2017. Interventions: Stage 0 patients (without enucleation) were given conservative therapy without a protocol. Stage I patients (with enucleation and no residual tumor) were divided into a high-risk group (retrolaminar invasion and/or scleral invasion) and a low-risk group (all remaining patients). High-risk children received adjuvant chemotherapy with 4 alternating cycles of regimen 1 (cyclophosphamide [65 mg/kg/d] [plus sodium-2-mercaptoethane sulfonate], idarubicin hydrochloride [10 mg/m2/d], and vincristine sulfate [0.05 mg/kg/d]) and 4 cycles of regimen 2 (carboplatin [500 mg/m2/d, days 1 and 2] and etoposide [100 mg/m2/d, days 1-3]). Low-risk children did not receive adjuvant therapy. Children with buphthalmia received neoadjuvant and adjuvant chemotherapy for a total of 8 cycles. Main Outcomes and Measures: Probability of event-free survival (extraocular relapse and death from any cause were considered events). Results: Among 187 children registered in the study, 175 were evaluable (92 [52.5%] female; median age, 22 months; age range, 3-100 months). Forty-two were stage 0 children, 84 were stage I low-risk children, and 42 were stage I high-risk children; there were 7 children in the buphthalmia group. With a median follow-up of 46 months, the 3-year probability of event-free survival was 0.97 (95% CI, 0.94-0.99), and the probability of overall survival was 0.98 (95% CI, 0.94-1.00). Stage 0 patients had no events, stage I low-risk patients had 1 event (orbital relapse treated with second-line therapy), stage I high-risk patients had 2 events (1 central nervous system relapse and 1 death from sepsis), and the buphthalmia group had 1 event (orbital relapse, followed by central nervous relapse and death). Conclusions and Relevance: Adjuvant therapy may be effective for high-risk unilateral retinoblastoma but is toxic, and neoadjuvant chemotherapy for buphthalmus appears feasible.

Advances in corneal stem-cell transplantation in rabbits with severe ocular alkali burns.

PURPOSE: To evaluate the efficacy of autologous corneal epithelial sheet implantation in restoring transparency of rabbit corneas severely injured by alkaline and the effect of photocoagulation in arresting corneal neovessel ingrowth. SETTING: Ophthalmology Department, School of Biomedical Sciences, Universidad Austral, Buenos Aires, Argentina. METHODS: Limbal stem-cell deficiency (LSCD) was induced in 14 rabbits by alkali burns. A limbal cell biopsy was done in the contralateral eye, and the cells were cultured on a fibroblast feeder layer grown on autologous clotted platelet-poor plasma or commercial fibrin for 21 days. Anterior keratectomy was followed by suturing corneal cell sheets over the stroma. If regrowth of vessels occurred, argon laser photocoagulation was applied to them. Rabbits were killed at 30, 60, 90, 180, and 360 days and the corneas processed for histopathology and inmunohistochemistry. RESULTS: A small (2.5 mm(2)) limbal biopsy achieved stem-cell replication in vitro. Corneal clarity and epithelial defects evolved with a trend toward improvement. There was a significant reduction in corneal neovascularization. Histology showed a multilayered stratified epithelium including several epithelial-like cells with clear cytoplasm in the deepest part. There were no signs of intraepithelial mucin cells on the implanted corneas. Immunohistochemical results showed expression of cytokeratins 3 and 12 in the central corneal epithelium and an absence of cytokeratin 19. CONCLUSIONS: Autologous limbal epithelial cell transplantation improved the corneal surface in eyes with LSCD. Photocoagulation of neovessel ingrowth was effective over the 1-year follow-up. Results may facilitate the application of this technique in patients.

Eyelid lymphoma in a patient with a gold weight implant. / Linfoma palpebral en paciente con implante de pesa de oro.

CASE REPORT: A male patient with an exposure keratopathy caused by lagophthalmos. A gold weight was implanted in the right upper eyelid. Eight months later, he presented with erythema and swelling of right upper eyelid. An incisional biopsy was performed, reporting extranodal marginal zone B cell lymphoma. DISCUSSION: when a tumour at the site of a gold weight implant is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis. Ocular adnexal lymphomas are relatively common. The presence of foreign material can cause chronic inflammation that could be the stimulus for the development of a lymphoproliferative disorder.

Surface and Orbscan II slit-scanning elevation topography in circumscribed posterior keratoconus.

We used an Orbscan II topography system (Bausch & Lomb) to study anterior and posterior surface abnormalities, keratometry, and topographic pachymetry in a patient with circumscribed posterior keratoconus. This system clearly showed a marked localized paracentral annular elevation in the posterior corneal surface that corresponded to an abrupt decrease in thickness and a slightly localized anterior surface bulge in the anterior float.

On the Cornea of Healthy Merino Sheep: A Detailed Ex Vivo Confocal, Histological and Ultrastructural Study.

Our study performed qualitative and quantitative studies on the corneal ultrastructure of healthy female Merino sheep of ages 4 months and 6 years old from the Argentinean Pampa. The corneas were evaluated using ex vivo laser-scanning confocal microscopy, light microscopy and transmission electron microscopy. Those studies allowed us to obtain detailed images of the corneal layers as well as quantitative data of the cellular and sub-basal nerve densities in the cornea from sheep of different ages. The density of the corneal cells was significantly different in the anterior versus the posterior epithelium and stroma. Moreover, the density of the epithelial, stromal cells and endothelial cells, as well as the sub-basal nerve density were significantly lower in adult than in young animals. Our work provided a wide-ranging description of the corneal ultrastructure of healthy female Merino sheep, which adds to the current knowledge about the ophthalmological aspects of this species and undoubtedly benefits veterinarians.

Intracellular inclusions in meningothelial meningioma. A histochemical and ultrastructural study.

This is a study on the histochemical and electron microscope findings of the intracellular inclusions in a case of meningothelial meningioma of the frontoethmoidal region with orbital involvement. The inclusions are PAS-positive, diastase resistant, and stain strongly positive with the modified Morel-Sisley reaction for protein-bound tyrosine and weakly with dihydroxy-dinaphthyl-disulfide (DDD) for the demonstration of sulfhydryl (SH) and disulfide (S-S) groups of proteins. These staining reactions suggest the inclusions are composed of conjugated proteins (glycoproteins). Ultrastructurally, the inclusions are located within intracellular spaces lined by microvilli and are composed of granular material, usually forming a dense core that is intermixed with small vacuoles. Numerous desmosomes and whorls of tonofibrils are concentrated around them. Our findings support the view that the intracellular inclusions, which are rarely found in meningiomas, represent an active secretory product of the meningothelial cells rather than a degenerative or phagocytic process.

Hemangiopericytoma of the orbit: a clinicopathologic study of 30 cases.

The clinical and pathologic features of 30 orbital hemangiopericytomas were reviewed. An effort was made to determine the clincopathologic characteristics that may correlate with the biologic behavior. Histopathologic criteria evaluated included degree of cellularity, nuclear atypia, mitotic activity, tumor size, and the presence of hemorrhage and necrosis. Histopathologically, 16 tumors were classified as benign, five as borderline, and nine as malignant. Follow-up information was obtained in 27 cases (mean duration of follow-up period was five and one-half years). Eight tumors recurred (30 per cent). Five patients died, four with widespread metastases (15 per cent) and one of unrelated causes. Tumors that recurred or metastasized were distributed among all three histologic groups. The interval between the onset of symptoms and metastasis for three of the four lethal tumors was 31 years, 28 years, and 8 1/2 years; in the fourth case it was unknown. For the entire series, the five-year actuarial survival rate was 89 per cent. Although the number of cases is too small to serve as a basis for firm conclusions, the lack of unequivocal correlation between the histologic features and clinical behavior is consistent with the unpredictable behavior of this neoplasm, as concluded by other investigators. Because of the apparent circumscription of most of these tumors, complete surgical excision rather than exenteration is recommended. Metastasis usually develops late in the clinical course of the disease, indicating that long-term follow-up studies are required before a cure can be assumed.

Benign fibrous tumor of the choroid.

A 32-year-old white woman presented with an amelanotic choroidal tumor in the left eye. Although a malignant melanoma could not be totally ruled out, some features suggested a benign tumor. The patient was followed up without treatment during a 2-year period. Neovascular glaucoma developed and the blind eye was enucleated. Histopathologic examination revealed a benign fibrous tumor of the choroid, presumably a fibrous histiocytoma.