Ocular surface squamous neoplasia - Review of etio-pathogenesis and an update on clinico-pathological diagnosis.

Ocular surface squamous neoplasia (OSSN) has a varied clinical presentation, the diagnosis of which rests on the histopathological examination of the excised lesion. The term OSSN includes mild dysplasia on one end of the spectrum and invasive squamous cell carcinoma on the other end. This lesion has a multi factorial aetiology with interplay of several factors like exposure to ultraviolet radiation, various chemical carcinogens and viral infections, however role of individual agents is not well understood. With the upsurge of infection with human immunodeficiency virus, a changing trend is seen in the clinical presentation and prognosis of patients of OSSN even in developed countries. Anterior segment optical coherence tomography (OCT) and confocal microscopy, hold promise in in-vivo differentiation of intraepithelial neoplasia from invasive squamous cell carcinoma. Variants of squamous cell carcinoma like Mucoepidermoid carcinoma, spindle cell carcinoma and OSSN associated with HIV infection should be suspected in a case of aggressive clinical presentation of OSSN or with massive and recurrent tumours. Surgery, chemotherapy and immunotherapy are the various treatment modalities which in combination show promising results in aggressive, recurrent and larger tumours.

Rapid intraoperative diagnosis of tumors of the eye and orbit by squash and imprint cytology.

PURPOSE: To evaluate the diagnostic accuracy of intraoperative squash and imprint cytologic techniques in ocular and orbital lesions. DESIGN: Observational case series. METHODS: Forty-five consecutive ocular and orbital biopsy specimens subjected to squash and imprint cytologic techniques for rapid intraoperative diagnosis were included in this study. The indications for which the surgeon requested intraoperative diagnosis included: (1) infiltrative lesions where a preoperative tissue diagnosis was not available, (2) discrepancy between preoperative and intraoperative clinical diagnosis, and (3) unusual clinical presentations with an uncertain diagnosis. Fresh unfixed tissue was used for making squash preparations and imprint smears. Alcohol-fixed smears were stained with hematoxylin and eosin, whereas air-dried smears were stained with the Giemsa stain. The residual tissue was subjected to routine processing for histopathologic examination. MAIN OUTCOME MEASURE: Correlation of intraoperative cytologic diagnosis with the final histologic diagnosis was the primary outcome measure. The correlation was considered to have complete concordance if the diagnosis matched with respect to nature of the lesion (benign vs. malignant) as well as with the further classification of the benign or the malignant lesion. Partial concordance was considered when there was agreement with respect to the nature of the lesion, but there was a mismatch in the further classification of the benign or the malignant lesion. RESULTS: Biopsies were obtained from 45 patients whose ages ranged from 1 to 79 years (median, 21 years). The sites of biopsy included eyelids (n = 4), conjunctiva (n = 6), intraocular tissue (n = 3), and orbit (n = 32). Adequate cellularity was obtained in all cases by squash and imprint techniques. A cytologic diagnosis could be made within 5 to 8 minutes after receiving the sample. Of 44 cases in which a cytologic diagnosis could be made, 21 (48%) were malignant and 23 (52%) were benign. Cytologic analysis was inconclusive in 1 case. The cytologic-histologic correlation showed complete concordance in 41 of 45 cases (91%) and partial concordance in 3 cases. Sensitivity and specificity of the squash and imprint technique in detecting malignant lesions was 100%. CONCLUSIONS: Assuming the availability of a skilled cytologist, ophthalmic pathologist, or both, squash and imprint preparations are useful for rapid and reliable intraoperative diagnosis of ocular and orbital lesions.

Late orbital recurrence of a choroidal melanoma following internal resection: report of a case and review of the literature.

The management of uveal melanomas always has been a challenge to the clinicians and has evolved from the era of eye-removing surgeries to elimination of the tumor by the body's own immune system through vaccines. Evaluating the outcome of each strategy improves our understanding of the disease process and helps us to improvise on the existing modalities of treatment. Internal resection of choroidal melanomas has been described as one of the treatment modalities for this malignant tumor. Tumor recurrences reported following this surgical procedure have been uncommon. We report a rare case of a 61-year-old Caucasian woman who presented with a 2-month history of progressive, painful proptosis in her right eye. Thirteen years ago she underwent internal resection of an intraocular choroidal melanoma in the same eye and had no evidence of metastatic disease. Magnetic resonance imaging demonstrated a mass occupying the superotemporal portion of the right orbit adjacent to the globe and behind the area of prior internal resection. Biopsy of the lesion and the subsequent A right orbital exenteration confirmed the diagnosis of recurrent malignant melanoma. Twenty-four months following exenteration the patient continues to be free of metastatic disease. Since internal surgical resection was described in 1984, this is the latest known recurrence of a posterior choroidal melanoma. In this review, we highlight the clinical features of this rare case and discuss in brief the rationale of various treatment modalities for choroidal melanoma.

Successful reconstruction of damaged ocular outer surface in humans using limbal and conjuctival stem cell culture methods.

When the ocular outer surface is badly damaged, subsequent corneal transplantation fails due to the absence of basal cells that are needed to support the graft. With the realization that the limbus and the conjunctiva have adult stem cells that can be cultured, it has been possible for us to explant culture these on de-epithelized human amniotic membrane, and to graft the resulting viable and transparent epithelium to 125 needy human patients with success. Ultrastructural, histological, biochemical and immunological assays establish the identity of the cells and the tissue formed.

Evaluation of agent and host factors in progression of mycotic keratitis: A histologic and microbiologic study of 167 corneal buttons.

PURPOSE: To evaluate the host and agent factors in the progression of mycotic keratitis through the microbiologic evaluation and histologic study of human corneal buttons obtained at the time of therapeutic keratoplasty. DESIGN: Retrospective noncomparative consecutive case series. MATERIALS: One hundred sixty-seven corneal buttons from 148 patients of microbiologically diagnosed and treated cases of mycotic keratitis who underwent therapeutic keratoplasty between January 1995 and May 1998. METHODS: Therapeutic penetrating keratoplasty, review of microbiologic results, histopathologic and microbiologic evaluation of the corneal buttons of mycotic keratitis MAIN OUTCOME MEASURES: Histologic evaluation of the buttons for morphologic changes, degree and distribution of inflammatory cells, presence or absence of fungal filaments, and their degree and distribution within the corneal buttons. RESULTS: The diagnosis of fungal infection was made on corneal scrapings in 36 cases; whereas in 131 (78%), the fungus was grown in cultures and identified as Aspergillus in 55 (42%), Fusarium in 42 (32%), unidentified hyaline fungi in 22 (17%), dematiaceous (unidentified) in 4 (3%), and others in 8 (6%). The mean interval between diagnosis and keratoplasty was 19 (+/-40) days. From the keratoplasty specimen, the fungus was identified at histologic examination in 127 of 167 (76%) buttons and grown by culture techniques in 76 of 115 (66%) buttons. The fungal species identified in the corneal button were Fusarium in 30 (39%); Aspergillus in 25 (33%); unidentified hyaline in 19 (25%), and others in 2 (3%). Fungus-positive corneal buttons had early surgery (mean, 15 days) compared with fungus-negative (39 days) corneal buttons (P = 0.0005), with 93% fungus positivity in the buttons removed within 2 weeks and 42% after 2 months. In the fungus-positive buttons, there was an inverse correlation between the degree, distribution of inflammatory cells, and fungal filaments (r = -0.255, P = 0.024; r = -0.199, P = 0.027), respectively. The factors necessitating an early keratoplasty were heavy fungal load, deeper penetration of fungus, and possibly insufficient inflammation to combat infection. A granulomatous reaction was noted in the posterior stroma and around the fragmented Descemet's membrane in 23 buttons (13.8%), independent of fungal species. Inflammation was unaffected by elimination of fungus and increasing interval between diagnosis and treatment. CONCLUSIONS: Rapid progression of mycotic keratitis in the early phases is by agent factors such as heavy load and deeper penetration of the fungus, insufficient inflammatory response, and possibly relative ineffectiveness of antifungal agents. Progression in the later phase of mycotic keratitis need not necessarily be agent mediated; it could be either host-modulated, species-related, or drug resistance, thereby suggesting that ideal treatment regimens should include sensitivity-based antifungal therapy aided by in vivo monitoring of fungal filaments.

Subepithelial amyloid deposits in congenital hereditary endothelial dystrophy: a histopathologic study of five cases.

PURPOSE: To report the clinical, histologic, ultrastructural, and immunohistochemical features of congenital hereditary endothelial dystrophy (CHED) associated with subepithelial amyloid deposits. METHODS: The clinical features of seven patients and histologic characteristics of eight corneal buttons were evaluated. The corneal specimens included five cases with histologic features of CHED associated with subepithelial amyloid. The remaining three corneal buttons of CHED without amyloid were obtained from the fellow eye of an affected patient and from siblings of two affected patients. Light microscopic studies were performed on sections stained with hematoxylin and eosin, periodic acid Schiff stain, and Congo red stain with and without permanganate bleach. Immunohistochemistry with an antibody to the amyloid AA protein and lambda and kappa light chains was done on all specimens. Electron microscopy was performed on three corneal specimens. The cases were followed for 1-9 years. RESULTS: The notable clinical findings included decreased vision, history of parental consanguinity (4/7 cases), and affected siblings (5/7 cases). Examination revealed nystagmus (5/7 cases) and bilateral ground-glass corneas in all patients. In addition, central subepithelial whitish opacities were noted in patients with CHED and amyloid. Three patients had associated congenital glaucoma. The patients underwent penetrating keratoplasty at a mean age of 10 years. Histologically, five corneal buttons of CHED revealed varying degrees of subepithelial amyloid deposits associated with a subepithelial fibrous pannus. Immunohistochemically, the deposits were nonreactive to anti-amyloid A antibody but were immunoreactive with an antibody to lambda light chains in two cases. Electron microscopy confirmed the presence of subepithelial amyloid. Thickening of Descemet's membrane and attenuation of corneal endothelial cells, noted in all cases, was consistent with features of CHED. The corneal buttons from the fellow eye and the siblings showed histologic features of CHED, with a subepithelial fibrous pannus without amyloid deposits. Spheroidal degeneration was noted in two corneal specimens. To date, no recurrence of the amyloid deposits has been seen in the grafts. CONCLUSIONS: This study demonstrates that subepithelial amyloidosis may be rarely associated with a recessive form of congenital hereditary endothelial dystrophy. The clinical, histologic, and immunohistochemical features suggest a secondary form of amyloidosis.

Ectopic brain presenting as orbital and conjunctival mass: A case report.

The presence of brain tissue in the orbit is a rare finding, whether it occurs isolated, in continuity with intracranial contents, or within a tumor. In this paper, the authors report a rare case of ectopic brain in the orbit, presenting as a conjunctival mass, in a 15-day-old female child. The clinical and histological features of the case are presented, together with a review of the literature.