Histopathological Study on the Proposed Pathogenesis of Intratarsal Keratinous Cysts.

PURPOSE: Intratarsal keratinous cysts (IKCs) are a recently described entity that is frequently misdiagnosed clinically as chalazia and mislabeled in the literature as "intratarsal epidermal inclusion cysts" or "epidermoid cysts." It is important to accurately diagnose IKCs and distinguish them from chalazia because IKCs require a complete surgical excision and can exhibit multiple recurrences following curettage. The authors performed a retrospective case series to further elucidate the pathogenesis of IKCs and to determine the diagnostically optimal panel of stains for diagnosis. METHODS: A study group of 8 specimens of IKCs and control specimens of epidermal inclusion cysts were obtained from their pathology laboratories. The authors compared the histological and immunohistochemical profile of IKCs and epidermal inclusion cysts by staining sections from each specimen with hematoxylin and eosin, periodic acid-Schiff, Masson trichrome, cytokeratin 5, cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen. The immunoreactivity data were then analyzed using a 2-tailed Mann-Whitney test, assuming a nonparametric population (p < 0.05 is significant). RESULTS: Histopathologically, IKCs are embedded in the tarsus lined by stratified squamous epithelium with an inner undulating cuticle filled with a compact keratinous-appearing material. The authors demonstrate that IKCs develop progressively from dilated meibomian ducts to the formation of complete cysts with their markers. The most valuable immunochemical stains to diagnose IKC were cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen (p < 0.05 with each). CONCLUSIONS: These findings provide a better understanding of the pathogenesis and the immunohistochemical findings of this relatively new entity allowing for more appropriate diagnosis of IKCs aiming to reduce future complications from their management.

Advanced glycation end products and diabetic retinopathy.

Retinopathy is a serious microvascular complication of diabetes and a major cause of blindness in young adults, worldwide. Early diabetic retinopathy is characterized by a loss of pericytes from retinal capillaries, the appearance of acellular capillaries and microaneurysms, and a breakdown of the blood-retinal barrier. In later stages, this can evolve into the proliferative phase in which there is neovascularization of the retina, which greatly increases the probability of vision loss. Advanced glycation end products (AGEs) which accumulate under hyperglycemic conditions are thought to play an important role in the pathogenesis of diabetic retinopathy. AGEs arise primarily by the modification of amine groups of proteins by reactive dicarbonyls such as methylglyoxal. Intracellular proteins including anti-oxidant enzymes, transcription factors and mitochondrial proteins are targets of dicarbonyl modification and this can modify their functional properties and thus compromise cellular physiology. Likewise, modification of extracellular proteins by dicarbonyls can impair cell adhesion and can generate ligands that can potentially bind to cell surface AGE receptors that activate pro-inflammatory signaling pathways. AGE inhibitors have been shown to provide protection in animal models of diabetic retinopathy and currently are being evaluated in clinical trials.

Bilateral necrobiotic xanthogranuloma of the eyelids followed by a diagnosis of multiple myeloma 20 years later.

A uniquely indolent case of necrobiotic xanthogranuloma with bilateral, periorbital involvement was presented. This patient presented with cutaneous eyelid lesions of 20 years' duration. Although symptomless, the patient underwent testing for hematologic malignancy, which led to a diagnosis of multiple myeloma. A review of the literature revealed that this is the longest interval between the onset of the skin manifestations and the diagnosis of the systemic malignancy in this rare disease.

Posterior Embryotoxon Revisited: An Immunohistologic Study.

PURPOSE: This series describes the immunopathologic features of posterior embryotoxon (PE) and demonstrates that it is not an anterior displaced Schwalbe's line as commonly described, but a peripheral corneal stromal nub variable in location with abnormal extracellular matrix. DESIGN: Case series. PARTICIPANTS: Archived specimens from patients with PE. METHODS: Sections from archived formalin-fixed, paraffin-embedded specimens (n = 9; 7 autopsy and 2 trabeculectomy specimens) were examined by light microscopy. Immunohistochemistry was performed on 5 specimens to characterize the extracellular matrix composition of PE. RESULTS: Posterior embryotoxon appeared as nubs of whorled collagen extending from the corneal stroma, lined in some instances, by Descemet membrane. These nubs were located anterior to Schwalbe's line (n = 4), posteriorly (n = 1), partially embedded in the trabecular meshwork (n = 1), or at Schwalbe's line (n = 2). Qualitatively, collagen I labeling of the PE stroma was similar or weaker than the corneal stroma, whereas collagen III staining was focal and slightly more intense compared with the corneal stroma. Lumican and keratan sulfate staining was similar or less intense in PE compared with the corneal stroma. MAIN OUTCOME MEASURES: Identify location of PE and its immunohistochemical features. CONCLUSIONS: In contrast to the widely accepted definition of PE as a prominent, anteriorly displaced Schwalbe line, histologic evidence suggests that it is a direct extension of the corneal stroma with variable locations that may displace the attenuated Descemet membrane when located anterior to or at Schwalbe's line. Immunohistochemical examination revealed that the composition of PE's extracellular matrix was similar to corneal stroma but with some variability in staining intensity.

Osseous metaplasia with formation of hematopoietic bone marrow in a blind, painful eye.

A 31-year-old woman underwent an evisceration of her blind, painful right eye with placement of an aluminum oxide orbital implant. Histopathologic assessment revealed functional hematopoietic bone marrow, confirmed by immunohistochemistry, within osseous metaplasia of the retinal pigment epithelium. This finding is exceedingly rare, with few cases reported in the English literature. This report raises numerous questions, including the association between pain and hematopoietic bone marrow formation, the potential benefits of hematopoietic bone marrow in the eye, and the molecular biologic basis for this rare phenomenon.

An Inflammatory Reaction to Stored Fascia Lata 37 Years Postimplantation.

We report a rare case of a suspected inflammatory reaction to stored fascia lata 37 years post-placement. Clinical, imaging, histopathological, and immunohistochemical findings are presented, with a literature review on reactions to stored fascia lata. A 39-year-old woman had upper eyelid congenital ptosis repaired successfully at 2 years with bilateral frontalis suspension procedures using stored fascia lata. Thirty-seven years later, the patient presented with swelling of her eyelids and forehead, which was tender to the touch, in the same pattern as the fascia lata slings placed earlier. Histopathological examination disclosed a non-necrotizing granulomatous inflammatory infiltrate with numerous asteroid bodies. Initially, it was responsive to oral prednisone, but with recurrent inflammation, long-term methotrexate was required to control the inflammation. To our knowledge, this type of delayed inflammatory reaction has not been previously reported. It raises a concern about the use of allogeneic donor tissue and accepted sterilization techniques that may not be 100% effective in deactivating all components of the donor graft, including potential infectious pathogens, leading to a subsequent latent reaction.

Lupus miliaris disseminatus faciei of the eyelids: report of two cases.

Lupus miliaris disseminatus faciei is a rare chronic, asymptomatic papular eruption, most commonly affecting the central face, including the eyelids. Our 2 patients presented with the typical clinical findings of small papular lesions in which histopathologic examinations disclosed granulomatous inflammation with necrosis associated with inflamed hair follicles. Except for its description as acne agminata by Duke-Elder in 1974, to the authors' knowledge, this condition has not been reported previously in the ophthalmic literature.

Infundibulocystic basal cell carcinoma of the eyelid in basal cell nevus syndrome.

PURPOSE: To describe the histopathologic findings in a series of eyelid basal cell carcinomas removed from patients with basal cell nevus syndrome. METHODS: Retrospective case series of 5 patients with basal cell nevus syndrome identified from our oculoplastics service. The systemic and ophthalmic features were reviewed, and a retrospective histopathologic analysis of all available previously excised eyelid lesions was performed. The pertinent published literature on basal cell nevus syndrome and eyelid basal cell carcinoma was reviewed. RESULTS: A total of 26 eyelid lesions were examined histopathologically. Twenty-three of these lesions were basal cell carcinomas. The infundibulocystic variant of basal cell carcinoma was identified most commonly (57%). CONCLUSIONS: Eyelid basal cell carcinomas in patients with basal cell nevus syndrome were commonly of the infundibulocystic variety in our series. Infundibulocystic basal cell carcinomas, which can be clinically indistinguishable from the more common forms, are thought to be less aggressive than other types of basal cell carcinoma and are a reassuring histopathologic diagnosis. It is important for the ophthalmologist and pathologist to be aware of infundibulocystic basal cell carcinomas, as they are more common in patients with basal cell nevus syndrome and may be a clue to the diagnosis of this autosomal dominant cancer-predisposition syndrome or other associated syndromes. To our knowledge, this variant of basal cell carcinoma has not been previously discussed in the ophthalmic literature.

Primary ductal adenocarcinoma of the lacrimal gland: A review and report of five cases.

Primary ductal adenocarcinoma (PDA) is a rare epithelial tumor of the lacrimal gland. Herein we report 5 cases and review 29 published cases of PDA of the lacrimal gland. Among these 5 cases, the most common clinical presentation was painless swelling and/or proptosis of their eye. The size of the lesions ranged from 1.6 to 2.5 cm. Histopathologic examination revealed proliferations of ductal or gland-like cells with vesiculated pleomorphic nuclei and prominent nucleoli. Tumor cells stained positive for epithelial and apocrine differentiation markers. Immunohistochemistry for human epidermal growth factor 2 was positive in 2 of the 4 cases. Four of the five patients were alive at the last follow-up visit. One died with bone metastases, which were diagnosed 25 months after exenteration and then survived an additional 51 months. On reviewing of twenty-nine previously published cases of PDA, the mean age of diagnosis was 58 years, with a male predominance (75%). Fifteen patients (54%) had distant metastases, 1 (4%) had local recurrence, and 10 (37%) suffered from a PDA-related death. PDA is a high-grade aggressive epithelial tumor of the lacrimal gland. Although rare, awareness and recognition of this malignancy are important to help determine prognosis and treatment options.

Osteogenesis with hematopoiesis simulating infection in a hydroxyapatite orbital implant.

A 28-year-old woman underwent secondary orbital implant surgery with placement of a hydroxyapatite implant. Over the next 7 years she underwent 3 drilling procedures. She began having copious discharge 1 year after the last drilling procedure. She was seen on numerous occasions with socket discharge, unresponsive to a variety of topical and oral antibiotics. Clinically, with the conjunctiva diffusely inflamed, the implant tender to touch, and the presence of a pyogenic granuloma, implant infection was suspected and the implant subsequently removed. Histopathologic assessment revealed widespread lamellar bone formation, including focal areas of marrow with active extramedullary hematopoiesis. There was no evidence of an inflammatory process or infection. Postoperatively the patient's symptoms and signs resolved. Extramedullary hematopoiesis within hydroxyapatite implants is rare. Porous orbital implant infection is also rare. Osteogenesis with extramedullary hematopoiesis simulating implant infection has not previously been reported.

Pilomatrixoma of the ocular adnexa: report of 3 cases with variations in the histopathological findings.

OBJECTIVE: To report the clinical and variations in the histopathological features of pilomatrixoma of the ocular adnexa in 3 young individuals. DESIGN: A retrospective case series was performed with clinical, histological, and immunohistochemical analysis. PARTICIPANTS: Case 1 is an 18-year-old male who presented with a reddish-blue swelling under the left eyebrow. The lesion measured 2 × 1 cm. Case 2 is a 2-year-old female who presented with a reddish-blue nodule inferior to the right eyebrow with telangiectatic vessels. The lesion measured 6 × 4 × 4 mm. Case 3 is a 14-year-old female who presented with a subcutaneous lesion under the right upper eyebrow with fluctuating inflammation. The lesion measured 12 × 3 × 2 mm. Histopathological examination of case 1 disclosed peripheral basaloid cells and central shadow cells containing calcific foci, separated by a transition zone. In case 2, histopathological analysis revealed central calcific foci in islands of shadow cells with more peripheral basaloid cells. In case 3, we observed numerous clusters of shadow cells with focal calcifications, as well as basaloid cells in a disorganized configuration. CONCLUSION: Pilomatrixoma is an uncommon benign skin neoplasm originating from the matrix of the hair root. We describe a spectrum of histopathological findings in pilomatrixoma of the ocular adnexal in 3 young individuals.

Immunohistochemical analysis of benign and malignant melanocytic lesions of the conjunctiva using double-staining.

OBJECTIVE: To implement a double-staining technique to identify the most sensitive and specific combinations of melanoma antigen recognized by T cells (Melan-A), microphthalmia-associated transcription factor (MITF), human melanoma black 45 (HMB45), and Ki67 aiming to assist in the diagnosis of atypical melanocytic conjunctival lesions that are more prone to malignant progression. METHODS: Eight specimens of conjunctival melanoma and of primary acquired melanosis with moderate to severe atypia were double-immunostained with a combination of a cytoplasmic marker (anti-Melan-A or anti-HMB45), and a nuclear marker (anti-MITF or anti-Ki67). Eight specimens of normal conjunctiva and of conjunctival nevi served as controls. The specimens were processed using 3,3-diaminobenzidine substrate for nuclear stains and the fast-red substrate for cytoplasmic stains. Each slide was analyzed by light microscopy and provided a percent scale and a 0 to 4+ score for each nuclear and cytoplasmic component. RESULTS: Melan-A and MITF were strongly positive markers for all melanocytic cells, whereas Ki67 and HMB45 provided a variable response for identifying potentially proliferative or aggressive cells. HMB45 and MITF proved to be the best combination for differentiating between atypical and benign lesions on a percent scale and a 0 to 4+ scale (p = 0.0004), with the 3 other combinations providing mainly confirmatory diagnostic information (p < 0.05). CONCLUSIONS: Our study used an immunohistochemical double-staining approach to differentiate between atypical and benign melanocytic lesions of the conjunctiva. Our findings should aid in a more complete immunohistopathological diagnosis of conjunctival melanocytic lesions, particularly in diagnostically difficult cases.

Regression of Sebaceous Carcinoma of the Eyelid after a Small Incisional Biopsy: Report of Two Cases.

PURPOSE: To report 2 cases of regression of sebaceous carcinoma of the eyelid after a small incisional biopsy. METHODS: Clinical, imaging, and histopathological findings are presented, with a literature review on regressing ocular tumors. RESULTS: Our first patient was a 79-year-old man who presented with a 10-month history of progressive left upper eyelid ptosis caused by an eyelid tumor with orbital involvement and confirmed on magnetic resonance imaging. Our second patient was a 70-year-old woman who presented with ptosis with a left upper eyelid mass. Both patients underwent a small incisional biopsy of their lesion. The histopathological diagnoses in both cases were consistent with sebaceous carcinoma. Both patients refused exenteration. Follow-up clinical examination and imaging disclosed total regression of the ptosis and of the neoplasm with no sign of recurrence in both patients over a 4-year period for Case 1 and a 7-year period for Case 2. CONCLUSION: Regression following incisional biopsy of basal cell, squamous cell, and Merkel cell carcinoma, including of the eyelid, is well documented. To the best of our knowledge, our 2 cases of sebaceous carcinoma are the first to be reported with total involution clinically and on imaging of the tumor following partial incisional biopsy.

Comparison of the incidence of opacification of Hydroview hydrogel intraocular lenses with the ophthalmic viscosurgical device used during surgery.

PURPOSE: To determine the effect of intraoperative ophthalmic viscosurgical devices (OVDs) on late opacification of the Hydroview hydrogel intraocular lens (IOL) (Bausch & Lomb Surgical). SETTING: Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada. METHODS: A retrospective study of 949 cases of Hydroview IOL implantations from February 1998 to September 2000 was conducted. Of the 949 implantations, 462 were performed by 1 surgeon (J.H.S.) using Viscoat (sodium chondroitin sulfate 4.0%-sodium hyaluronate 3.0%) and 487 were performed by a second surgeon (W.A.N.) using Biolon (sodium hyaluronate 1.0%). Surgical techniques were identical with the exception of surgeon OVD preference. The number of IOLs opacifying and requiring explantation was determined in each group. RESULTS: Seventy-one Hydroview IOLs had surface calcification deposits that presented a mean of 39 months postoperatively. Twenty-two IOLs opacified sufficiently to warrant a recommendation of IOL explantation; 20 IOLs were explanted, and 2 surgeries were cancelled due to death or disability. In all cases of opacification, Viscoat had been used intraoperatively. This represented a 15.4% incidence of opacification in the Viscoat group, with 31.0% cases severe enough to warrant a recommendation of explantation. CONCLUSION: The results suggest that the intraoperative use of Viscoat has a facilitating role in the development of late calcification and opacification of the Hydroview IOL.

Acanthamoeba keratitis: persistent organisms without inflammation after 1 year of topical chlorhexidine.

PURPOSE: To report a non-contact lens wearer with persistent Acanthamoeba organisms in the cornea after being treated with medical therapy that included topical chlorhexidine as 1 agent for 1 year. METHODS: A 53-year-old man with Acanthamoeba keratitis was treated with medical therapy for >1 year, followed by a penetrating keratoplasty. RESULTS: Histopathologic examination of the keratoplasty specimen revealed viable-appearing Acanthamoeba cysts and trophozoites within the deep corneal stroma in a focus of corneal scarring. CONCLUSIONS: The use of chlorhexidine as 1 agent in the medical management of Acanthamoeba keratitis may not eradicate the organisms.

Medial canthal tophus.

A 68-year-old-man was seen in consultation for a suspicious medial canthal lesion that developed over a 2-year period. The raised, nodular lesion was skin colored, had a raised pearly border and a central depression with superficial crusting. Basal cell carcinoma was suspected and an excisional biopsy was performed. However, a granulomatous inflammatory process with features consistent with gout was identified. Further inquiry confirmed a history of gout including prior tophi on each elbow. Gouty tophi are extremely rare in the periocular area but should be considered in the differential diagnosis of basal cell carcinoma as they may have a similar clinical appearance.

Primary localized conjunctival amyloidosis simulating a lymphoproliferative disorder.

A 39-year-old previously healthy woman presented with a 3-year history of a painless lump in her left upper eyelid that had been increasing in size over the last 8 months. On examination, a soft, nontender mass was palpated in the medial left upper eyelid and anterior orbit. She had 2 mm of eyelid ptosis and 2 mm of inferior globe displacement. A salmon-pink mass of tissue was identified in the superomedial conjunctiva. The remaining ophthalmic examination was unremarkable. A lymphoproliferative process was suspected; however, an incisional biopsy revealed amyloid. Further workup showed no evidence of systemic amyloidosis, lymphoma, plasmacytoma, or multiple myeloma. The patient has been followed for more than 16 months with no new developments in her health. Amyloidosis has a variety of presentations in the periocular region and may be the sole manifestation of the disease process. It is not often considered in the differential diagnosis of conjunctival lesions. The classic "salmon-pink" conjunctival infitrate has been associated with lymphoproliferative disorders; however, amyloid should also be considered, as it may be clinically indistinguishable.

Histopathology in a dissecting conjunctival filtering bleb.

CASE REPORT: Four years after trabeculectomy, a patient developed unilateral tearing and presented with an ipsilateral conjunctival filtering bleb that had dissected into the cornea. The corneal portion of the bleb was excised for symptomatic relief. Histopathological examination disclosed dissection of the conjunctival filtering bleb into the cornea between Bowman's layer and the corneal epithelium. The internal portion of the bleb consisted of loose stromal tissue lacking any internal epithelial lining. COMMENTS: A conjunctival bleb dissecting into the cornea is a well-described late complication of trabeculectomy; however, its pathophysiology remains controversial. The subepithelial dissection plane in this specimen supports the concept that the conjunctival filtering bleb may dissect into, as well as "overhang", the limbal cornea.

Generalized posterior keratoconus: clinical pathologic correlations.

CASE REPORT: A 73-year-old woman presented with bilateral generalized posterior keratoconus. The corneal thickness measured 0.320 mm paracentrally and 0.440 mm toward the periphery. The corneal specimen revealed absence of Bowman's layer and focal homogeneous oval stromal deposits that stained for amyloid. COMMENTS: Our case of generalized posterior keratoconus shows absence of Bowman's layer. The amyloid deposits, which also were noted clinically in the cornea of the fellow right eye, were most consistent with a diagnosis of polymorphous amyloid degeneration. To our knowledge, this is the first histopathological report of generalized posterior keratoconus.