Dedifferentiated liposarcoma of the orbit.

Purpose: To present a rare case of dedifferentiated liposarcoma of the orbit. Observations: A 61-year-old male complained of left-sided proptosis, diplopia, and limited ocular motility for two years. Biopsy results at that time were suggestive of an atypical lipomatous neoplasm. Ten years later, he presented with increase in size of the mass and worsening of his symptoms. Imaging showed a multi-lobulated mass in the left orbit involving the intraconal, medial, and anterior orbit. Decompression and orbitotomy with biopsy were performed to debulk the mass. Pathology showed a low-grade well-differentiated liposarcoma and the patient was monitored thereafter annually. Eight years later, he complained of persistent proptosis and mass effect from the tumor resulting in ptosis and diplopia and underwent orbital exenteration. Histopathological analysis of the exenterated orbit revealed a focal area of dedifferentiated liposarcoma. Conclusions and importance: Dedifferentiation of an orbital mass can occur as a late complication years after the diagnosis of well-differentiated liposarcoma. Compared to the previously published cases of orbital liposarcoma, this presentation shows a prolonged timeline prior to dedifferentiation (18 years after initial diagnosis). Symptoms of growth or invasive features could indicate dedifferentiation and should warrant a biopsy.

Dendritic Melanocytic Hyperplasia in Pterygia: A Potential Source of Diagnostic Confusion with Primary Acquired Melanosis.

Introduction: The aim of this study was to report the nearly ubiquitous prevalence of melanocytic hyperplasia in benign pterygia/pingueculae and establish that the entity is insufficiently recognized. Methods: This is a retrospective immunohistochemical pathology case series of 30 consecutive pterygia/pingueculae samples selected from an ophthalmic pathology database at a single institution. Histopathologic and immunohistochemistry analyses with anti-SOX-10 and anti-MART-1 antibodies were used for identifying melanocytes. The number of squamous cells intervening between melanocytes was determined. Results: The frequency of dendritic melanocytes was found to meet the criteria for dendritic melanocytic hyperplasia in 29 of 30 pterygia/pingueculae samples using specific antibodies. Melanocytes were found in several patterns: diffuse (28%), multifocal (28%), and focal (44%). In each case, the melanocytes were distributed as single melanocytes at the base; clusters of melanocytes were seen in 17% of samples. There were an average of about two intervening epithelial cells between melanocytes at the base. Conclusion: When diagnosed with immunohistochemistry, dendritic melanocytic hyperplasia is nearly ubiquitous in pterygia and pingueculae. Melanocytic hyperplasia may have a distribution that includes nests and single melanocytes above the basal layer, which can be confused with forms of primary acquired melanosis. It is important for pathologists to recognize these lesions as a distinct benign clinicopathologic entity.

Low-grade fibromyxoid sarcoma of the orbit.

A 70-year-old male presented with diplopia and painless proptosis of the left eye for 5 months. Examination showed 6 mm of axial proptosis and restriction of supraduction, abduction and adduction, and mild limitation of infraduction of the left eye. Magnetic resonance imaging demonstrated a large, moderately well-circumscribed intraconal mass in the left lateral orbit, and excisional biopsy was performed. Histopathologic features of mixed fibrous and myxoid areas in a whorl-like pattern and immunohistochemical staining for MUC4 confirmed the diagnosis of low-grade fibromyxoid sarcoma (LGFMS). Next-generation sequencing revealed genetic fusion of EWSR1-CREB3L1. LGFMS is an extremely rare neoplasm with only two prior documented cases of orbital involvement. Here, we report the third case of orbital LGFMS.

Late Onset Interface Calcium Deposition After Laser In Situ Keratomileusis.

PURPOSE: The purpose of this study was to report a novel clinical entity characterized by bilateral calcium deposits in the flap interface after uncomplicated laser in situ keratomileusis (LASIK). METHODS: Slit-lamp examination, anterior segment optical coherence tomography imaging, and histopathologic analysis of an interface opacity were performed to characterize and identify the origin of the interface opacities. RESULTS: Two unrelated healthy young men who underwent LASIK in both eyes at 20 (case 1) and 44 (case 2) years of age were diagnosed with bilateral, white anterior stromal opacities 5 years after LASIK surgery. Slit-lamp examination and anterior segment optical coherence tomography imaging demonstrated that the opacities were located at the level of the LASIK interface in both eyes of both cases, with most of the opacities located at the temporal edge of the flap in each eye of case 2. An opacity from case 2 demonstrated birefringence using polarization microscopy and staining with Alizarin red, indicative of calcium deposition. The serum calcium level was borderline elevated in case 1 and within normal limits in case 2. CONCLUSIONS: Intrastromal calcium deposition can occur after LASIK surgery, with the deposits resembling dystrophic deposits located in the LASIK flap interface in individuals with granular corneal dystrophy type 2. Because the etiology and management of calcific and dystrophic interface deposition after LASIK are distinct, it is important for clinicians to differentiate the 2 entities based on the examination, diagnostic imaging, and, if necessary, molecular genetic analysis.

Tear Lipocalin and Lipocalin-Interacting Membrane Receptor.

Tear lipocalin is a primate protein that was recognized as a lipocalin from the homology of the primary sequence. The protein is most concentrated in tears and produced by lacrimal glands. Tear lipocalin is also produced in the tongue, pituitary, prostate, and the tracheobronchial tree. Tear lipocalin has been assigned a multitude of functions. The functions of tear lipocalin are inexorably linked to structural characteristics that are often shared by the lipocalin family. These characteristics result in the binding and or transport of a wide range of small hydrophobic molecules. The cavity of tear lipocalin is formed by eight strands (A-H) that are arranged in a ß-barrel and are joined by loops between the ß-strands. Recently, studies of the solution structure of tear lipocalin have unveiled new structural features such as cation-π interactions, which are extant throughout the lipocalin family. Lipocalin has many unique features that affect ligand specificity. These include a capacious and a flexible cavity with mobile and short overhanging loops. Specific features that confer promiscuity for ligand binding in tear lipocalin will be analyzed. The functions of tear lipocalin include the following: antimicrobial activities, scavenger of toxic and tear disruptive compounds, endonuclease activity, and inhibition of cysteine proteases. In addition, tear lipocalin binds and may modulate lipids in the tears. Such actions support roles as an acceptor for phospholipid transfer protein, heteropolymer formation to alter viscosity, and tear surface interactions. The promiscuous lipid-binding properties of tear lipocalin have created opportunities for its use as a drug carrier. Mutant analogs have been created to bind other molecules such as vascular endothelial growth factor for medicinal use. Tear lipocalin has been touted as a useful biomarker for several diseases including breast cancer, chronic obstructive pulmonary disease, diabetic retinopathy, and keratoconus. The functional possibilities of tear lipocalin dramatically expanded when a putative receptor, lipocalin-interacting membrane receptor was identified. However, opposing studies claim that lipocalin-interacting membrane receptor is not specific for lipocalin. A recent study even suggests a different function for the membrane protein. This controversy will be reviewed in light of gene expression data, which suggest that tear lipocalin has a different tissue distribution than the putative receptor. But the data show lipocalin-interacting membrane receptor is expressed on ocular surface epithelium and that a receptor function here would be rational.

Pathologic Study of Supernumerary Orbital Band in Type I Duane Syndrome.

BACKGROUND/AIMS: Accessory orbital bands are relatively rare and very few reports detail histopathology. Cases in the literature describe the composition of the bands as muscular and/or fibrous. The composition of the supernumerary band lying deep in the medial rectus muscle in a patient with type I Duane syndrome was investigated. METHODS: Histochemical stains were used in conjunction with polarized light for differentiating compressed collagen from muscle. Immunohistochemistry was used for verification of the presence of muscle. RESULTS: Compressed collagen appeared red using Masson trichrome staining. Collagen was positively identified by illumination with polarized light on several stains including the underutilized Sirius red dye. CONCLUSIONS: The findings of dense collagen fibers in the fibrotic band with focal striated muscle correlated with the restrictive strabismus. In concert with other cases in the literature, it is proposed that the fibrous bands are generally associated with restrictive strabismus. Bands that are muscular may or may not be associated with strabismus. Special techniques are needed to positively identify compressed collagen.

Correlation of Immunocytochemistry of BRCA1-associated Protein-1 (BAP1) With Other Prognostic Markers in Uveal Melanoma.

PURPOSE: Prior studies have shown that nuclear reactivity for BRCA1-associated protein-1 (BAP1) yields prognostic information for paraffin-embedded uveal melanomas. Lacking are immunocytochemical studies of BAP1 on fine needle aspiration biopsies of uveal melanoma that correlate with prognosis or other markers of prognosis. Our purpose was to fill this gap. DESIGN: Experimental laboratory study. METHODS: Fine needle aspiration biopsies were performed prospectively on 113 patients with uveal melanomas, garnering limited subsets of cases for comparison. Agreement between immunocytochemistry for BAP1 nuclear staining vs chromosome 3 ploidy analysis and gene expression profiling was assessed by 2 × 2 contingency table analysis. RESULTS: The presence or absence of suppression of nuclear expression of BAP1 was strongly associated (73%, P = .000002) with monosomy and disomy chromosome 3, respectively. BAP1 nuclear expression was also correlated with gene expression profiling. Chromosome 3 ploidy analysis correlated with gene expression profiles. CONCLUSION: When adequate material is obtained, immunocytology using BAP1 is a potentially informative tool for prognostication of uveal melanoma.

Orbital granulomatosis with polyangiitis masquerading as invasive fungal sinusitis.

A 55-year-old man presented with unilateral orbital inflammation and no light perception vision. Imaging revealed infiltrative enhancement of the optic nerve, orbit, and intracranial tissue. The case was suspicious for invasive fungal disease, but ultimate workup and orbital biopsy revealed granulomatosis with polyangiitis. The patient's inflammation resolved with corticosteroid and rituximab therapy. Granulomatosis with polyangiitis is a systemic vasculitis that can mimic a number of orbital pathologies.

Aggressive necrotizing pseudomonal sinonasal infections.

BACKGROUND: Pseudomonas aeruginosa is a gram-negative bacterium frequently implicated in recalcitrant sinonasal infections, especially in immunocompromised hosts. We report 6 cases of rapidly progressive pseudomonal acute rhinosinusitis producing tissue necrosis and, in certain cases, cranial nerve palsies. METHODS: Retrospective review of 6 patients with aggressive necrotizing sinonasal infections treated at 4 tertiary academic medical centers with sinonasal cultures growing P. aeruginosa in the absence of other pathology. RESULTS: A total of 6 patients were identified. In all cases, there was tissue necrosis that appeared to mimic an invasive process such as mucormycosis, prompting urgent surgical intervention. Pathologic analysis revealed fibropurulent exudates in backgrounds of positive P. aeruginosa cultures without evidence of invasive fungal organisms or malignancy. Four of the 6 patients presented with cranial nerve palsies, with 3 patients having vision changes and 3 complaining of trigeminal neuropathy. Four of 6 patients improved clinically over time after surgery and antibiotic therapy; 1 remains in follow-up without complete improvement and 1 has succumbed to other causes. CONCLUSION: P. aeruginosa is a tenacious organism that is frequently associated with severe, recalcitrant sinonasal infections. We report the first case series of necrotizing sinonasal infections caused by this organism, and illustrate that, in rare cases, P. aeruginosa may mimic and behave like life-threatening conditions such as fulminant invasive fungal sinusitis or malignancy.

Necrotizing Tenon's capsule infection in a lymphopenic Down syndrome patient following strabismus surgery.

Periocular infection is a rare complication of strabismus surgery. We describe a case of necrotizing Tenon's capsule infection after uncomplicated strabismus surgery in a boy with Down syndrome and blepharitis. Pathologic diagnosis was severe acute necrotizing inflammation with Gram positive coccal forms. Resolution of infection occurred after surgical debridement and intravenous and topical antibiotics. Work-up revealed lymphopenia related to Down syndrome. Patients with Down syndrome may have risk factors for postoperative infection including blepharitis and immunologic abnormalities.

Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity.

BACKGROUND: Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry. MATERIALS AND METHODS: Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis. RESULTS: A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjunctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant. CONCLUSIONS: HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID.

Variable Results for Uveal Melanoma-Specific Gene Expression Profile Prognostic Test in Choroidal Metastasis.

IMPORTANCE: We report our experience with uveal melanoma-specific gene expression profile (GEP) testing on a series of choroidal metastatic tumors confirmed by cytopathology so that clinicians may be aware that receiving a class 1 or class 2 test result in nonmelanoma is possible. OBSERVATIONS: Retrospective review of all cytopathology and DecisionDx-UM GEP reports between January 2012 to December 2014 from intraoperative fine-needle aspiration biopsy of choroidal tumors undergoing brachytherapy. Four patients were identified to have cytopathology consistent with a nonmelanoma primary. All 4 patients presented with a unilateral, single choroidal tumor, which was treated with iodine-125 brachytherapy and underwent intraoperative fine-needle aspiration biopsy for cytopathology and uveal melanoma-specific GEP testing for molecular prognostication. Gene expression profile testing of the choroidal tumor in each patient revealed class 1A in 3 patients and class 2 in 1 patient. CONCLUSIONS AND RELEVANCE: DecisionDx-UM GEP may be a helpful test for molecular prognostication in patients with uveal melanoma; however, class 1 and class 2 test results are indeed possible in the setting of a nonmelanoma malignancy. We recommend that cytopathology and/or other melanoma-specific testing be performed in all cases of suspected choroidal melanoma because GEP with this assay is unable to rule out the diagnosis of a choroidal melanoma.

Antibacterial activity of rifamycins for M. smegmatis with comparison of oxidation and binding to tear lipocalin.

A mutant of Mycobacterium smegmatis is a potential class I model substitute for Mycobacterium tuberculosis. Because not all of the rifamycins have been tested in this organism, we determined bactericidal profiles for the 6 major rifamycin derivatives. The profiles closely mirrored those established for M. tuberculosis. Rifalazil was confirmed to be the most potent rifamycin. Because the tuberculous granuloma presents a harshly oxidizing environment we explored the effects of oxidation on rifamycins. Mass spectrometry confirmed that three of the six major rifamycins showed autoxidation in the presence of trace metals. Oxidation could be monitored by distinctive changes including isosbestic points in the ultraviolet-visible spectrum. Oxidation of rifamycins abrogated anti-mycobacterial activity in M. smegmatis. Protection from autoxidation was conferred by binding susceptible rifamycins to tear lipocalin, a promiscuous lipophilic protein. Rifalazil was not susceptible to autoxidation but was insoluble in aqueous solution. Solubility was enhanced when complexed to tear lipocalin and was accompanied by a spectral red shift. The positive solvatochromism was consistent with robust molecular interaction and binding. Other rifamycins also formed a complex with lipocalin, albeit to a lesser extent. Protection from oxidation and enhancement of solubility with protein binding may have implications for delivery of select rifamycin derivatives.

Aggressive Low-Grade Optic Nerve Glioma in Adults.

Primary optic nerve gliomas are most commonly benign pilocytic astrocytomas (World Health Organization [WHO] Grade I) occurring in childhood and following an indolent course. Malignant optic gliomas occur in adulthood and follow an extremely aggressive course, with rapid infiltration of the chiasm, blindness, and death typically within months. A third category of optic glioma, occurring in adulthood, histopathologically benign (WHO Grade I-II) but following an aggressive course, has been rarely reported. The authors describe clinical and histopathologic features of clinically aggressive but histopathologically benign optic nerve gliomas of adulthood. Retrospective review of cases of biopsy-proven optic nerve glioma in the neuro-ophthalmology division of the Jules Stein Eye Institute from 1990 to 2011 was carried out. Cases following an aggressive course were selected for review of clinical, neuroradiologic, and histopathologic features. Three cases were selected for detailed study. Ages ranged from 31 to 45 years. All were initially diagnosed with optic nerve inflammation or benign neoplasm based on clinical and neuroradiologic features, but all suffered neuroradiologic extension and rapid deterioration of vision in the affected eye to no light perception over 3-8 weeks. Optic nerve biopsies were undertaken for the suspicion of malignancy. Features ranged from WHO Grade I (pilocytic astrocytoma, ganglioglioma) in two cases, to WHO Grade II in one case (diffuse astrocytoma, histopathologically benign, but associated with aggressive features such as high p53 [13-21%] and Ki-67 [40%]). The diffuse astrocytoma case subsequently developed extensive intracranial extension suspicious for malignant transformation. These findings indicate that benign optic nerve glioma in adults may be initially misdiagnosed as inflammation, be clinically aggressive, and require excision to prevent further intracranial involvement.

Parotidectomy and neck dissection in the management of conjunctival melanoma: are they necessary?

OBJECTIVES/HYPOTHESIS: The objectives of this study were to review traditional techniques for the management of conjunctival melanoma and assess the need for parotidectomy and neck dissection in the management of conjunctival melanoma. STUDY DESIGN: Retrospective review. METHODS: This study was a retrospective review conducted in a tertiary academic medical center of patients diagnosed with conjunctival melanoma over a 20-year period RESULTS: There were 39 patients diagnosed with conjunctival melanoma identified from January 1990 to December 2010. Follow-up varied from 2 to 201 months (median, 25 months). Of the patients, 16 (41%) had local recurrences at the primary site, two (13%) of whom later presented with parotid disease. One patient with parotid recurrence had a subsequent neck dissection for confirmed metastatic spread. No patient in this series had metastatic cervical disease without initial spread to the parotid. The probability of disease-free survival at 1, 2, and 5 years was 77%, 68%, and 50%, respectively. The probability of parotid free progression at 1, 2, and 5 years was 100%, 96%, and 90%, respectively. CONCLUSIONS: Conjunctival melanoma is a rare malignancy traditionally managed with aggressive treatment to optimize local control. The role for staging parotidectomy with or without neck dissection has been heavily debated. Based on our review, parotidectomy only needs to be undertaken when high suspicion for metastatic spread is present, such as a palpable or radiographically evident mass. In addition, without documented parotid disease, neck dissection is not required.

Microbiologic and histopathologic assessment of corneal biopsies in the evaluation of microbial keratitis.

PURPOSE: To investigate the utility of corneal biopsy in the evaluation of infectious keratitis; to compare results of culture and histopathologic examination of the same specimens; to investigate potential factors related to positive biopsy results. DESIGN: Retrospective, observational case series. METHODS: We reviewed medical records for all patients who underwent corneal biopsy because of infectious keratitis at the Jules Stein Eye Institute from June 1989 through June 2009. In general, biopsy specimens were both cultured and examined histopathologically. Lesion size, lesion progression, and interval from presentation to biopsy were analyzed as possible predictors of positive biopsies. RESULTS: Organisms were identified in 20 of 48 (42%) consecutive biopsies (positive cultures in 9 of 47 cases [19%]; positive histopathologic examination in 19 of 47 cases [40%]). Culture and histopathologic results were concordant in 30 of 46 biopsies (65%) for which both techniques were performed; 10 of the 16 discordant cases were culture-negative/histopathology-positive, while the remaining 6 had positive but discordant results for the 2 techniques (cultures all showed bacteria; histopathologic examination showed fungi or cysts consistent with Acanthamoeba sp.). Corneal biopsy revealed microorganisms in 12 of 27 patients (44%) with negative cultures of corneal scrapings obtained at presentation. None of the potential risk factors was statistically associated with positive biopsies. CONCLUSIONS: Corneal biopsy can be useful for identifying the cause of infectious keratitis in selected cases. Culture and histopathologic examination can provide complementary information, but discordant results may occur. Acanthamoebic and fungal infections are more likely to be identified by histopathologic examination.

MUC16 as a sensitive and specific marker for epithelial downgrowth.

OBJECTIVE: To compare immunohistochemical results of cytokeratin AE1/AE3, the traditional favored marker, with MUC16 and cytokeratin 19 for diagnostic sensitivity and specificity in epithelial downgrowth and control corneas. METHODS: Immunohistochemical analysis was performed in 5 cases of epithelial downgrowth and 5 control specimens for MUC16, cytokeratin AE1/AE3, and cytokeratin 19 using the immunoperoxidase method. The mean percentages of reactive cells on the epithelium and endothelium were compared for each antibody using the Wilcoxon rank sum test. The sensitivity and specificity for each marker were compared. RESULTS: All 3 antibodies showed high sensitivity (100%) in identifying epithelial downgrowth. However, the specificity was greatest for MUC 16 (100%) compared with cytokeratin 19 (80%) and cytokeratin AE1/AE3 (0%). None of the endothelial cells in any case showed reactivity to anti-MUC16 compared with anti-cytokeratin AE1/AE3 (mean [SD], 0.0% [0.0%] vs 17.4% [10.4%]; P = .008). Cytokeratin 19 was positive in every case of epithelial downgrowth but showed focal staining of the endothelium (3.4% of cells) in 1 control. CONCLUSIONS: Antibodies for MUC16, cytokeratin AE1/AE3, and cytokeratin 19 are equally sensitive for downgrowth. However, anti-MUC16 showed superior specificity compared with anti-cytokeratin 19 or anti-cytokeratin AE1/AE3 in this study.

Microcornea, posterior megalolenticonus, persistent fetal vasculature, and coloboma: a new syndrome.

PURPOSE: To report a newly identified syndrome of bilateral microcornea, posterior megalolenticonus, persistent fetal vasculature, and chorioretinal coloboma (MPPC). DESIGN: Noncomparative case series. PARTICIPANTS: Eight patients with MPPC syndrome. METHODS: Clinical data collected retrospectively included visual acuity, findings on office examination as well as examination under anesthesia, and, in some cases, fluorescein angiography. Intraoperative findings and postoperative visual acuity and clinical findings were recorded when surgical intervention was performed. MAIN OUTCOME MEASURES: Clinical description, intraoperative findings, and surgical outcomes. RESULTS: All patients were found to have microcornea with corneal diameters of less than 8 mm. In all cases, the crystalline lens was found to be retrodisplaced with massive enlargement and a dramatic posterior lenticonus (posterior megalolenticonus), and the ciliary processes frequently were drawn to the lens capsule. A stalk of persistent fetal vascular tissue extended from the posterior pole of the lens to the optic disc. Posterior chorioretinal coloboma was present in all cases. Some cases also exhibited grossly dysplastic retina. Presentation frequently was asymmetric. Eight eyes of 6 patients underwent lensectomy, vitrectomy, membrane peeling, and fluid-Healon exchange (Healon OVD [sodium hyaluronate]; Advanced Medical Optics, Santa Ana, CA) with functional vision in at least 4 of the 5 patients with postsurgical follow-up. CONCLUSIONS: Bilateral microcornea, posterior megalolenticonus, persistent fetal vasculature, and chorioretinal coloboma syndrome is a distinct syndrome previously unreported, to the authors' knowledge, and appropriate surgical intervention may result in significantly improved visual function.

Epstein-Barr virus-associated smooth muscle tumor of the iris in a patient with transplant: a case report and review of the literature.

Epstein-Barr virus infection has been linked to the development of smooth muscle tumors in immunocompromised patients with organ transplants and acquired immunodeficiency syndrome. A 52-year-old female recipient of a renal transplant presented with enlarging masses of the left iris. Incisional biopsy of the mass revealed a smooth muscle tumor of the iris. Epstein-Barr virus infection was confirmed by in situ hybridization for Epstein-Barr virus-encoded, small RNA in tumor cells. Eight months after total iridectomy the patient was free of disease. Although the prognosis and classification of Epstein-Barr virus-associated smooth muscle tumors are controversial, mortalities caused by these tumors are rare.