Silent squamous cell carcinoma invading the orbit following the course of the zygomaticotemporal nerve.

PURPOSE: To evaluate the clinical and histopathological characteristics of silent skin squamous cell carcinomas (SCC) with invasion routes to the orbit. METHODS: Retrospective case studies. Clinical records and histopathological material, therapy and complications were evaluated, together with MRI imaging analyses and literature review on the anatomy of the lateral orbital wall in relation to the zygomatico-temporal nerve channel. RESULTS: Two recent cases of metastatic SCC from het lateral zygomatic region to het orbit are reported. Originally the skin tumors of the first case was diagnosed as benign, but a review of the pathology of these skin tumors showed an invasive SCC. The second case was diagnosed as an atypical SCC. Analysis of possible invasion routes, using both computer tomography (CT) and magnetic resonance imaging (MRI), indicated neither skin nor bone involvement. However, the lateral temporal fossa near the entrance of the zygomatico-temporal channel showed small tumors and pseudo-cysts. The original skin tumor specimens did not show malignant tissue in the surgical margins nor intra- or perineural invasion. CONCLUSIONS: Because the course of the zygomatico-temporal nerve bundle was exactly in line with the original skin tumor, the channel and the orbital tumors, this route should be considered when malignant orbital tumors have a history of or a relation with a periorbital skin-tumor.

Anterior segment optical coherence tomography and ultrasound biomicroscopy for measuring thickness of corneal and bulbar conjunctival tumours.

BACKGROUND/OBJECTIVE: Anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) are two non-invasive imaging techniques used for the measurement of tumour thickness in corneal and bulbar conjunctival tumours. Histopathology (HP), however, remains the gold standard for the measurement of tumour thickness. The aim of this study was to determine whether AS-OCT and UBM are as accurate as HP for measuring tumour thickness. METHODS: Forty-two corneal and bulbar conjunctival tumours were imaged using AS-OCT and UBM. Images were assessed and tumour thickness was measured. Eleven patients subsequently underwent surgical excision. All specimens were measured during histopathological analysis. The correlation of the thickness measurement on HP to AS-OCT and UBM was then statistically analysed. In cases where the tumour was not excised, thickness measurement comparisons between AS-OCT and UBM were analysed. RESULTS: AS-OCT and UBM measurements of tumour thickness were found to be significantly positively correlated (p=<0.001), as were UBM and HP thickness measurements (p=0.031). HP and AS-OCT measurements, however, only showed a mild but non-significant positive correlation. CONCLUSION: Both AS-OCT and UBM are useful techniques to image and measure the thickness of corneal and conjunctival bulbar tumours. While AS-OCT provides better details than UBM, it was more limited in visualising the posterior boundary of the tumour, particularly in malignant tumours. While thickness measurements of both methodologies were correlated, neither should yet be considered as replacements to the gold standard of HP.

Management of conjunctival melanoma with local excision and adjuvant brachytherapy.

BACKGROUND/OBJECTIVES: To evaluate the management of conjunctival melanoma with local excision and adjuvant brachytherapy. SUBJECTS/METHODS: Data of all patients who received local excision and adjuvant brachytherapy for conjunctival melanoma between 1999 and 2016 in a Dutch national referral centre were reviewed. A protocol with Sr-90 was used until 2012, a protocol with Ru-106 was used hereafter. Local recurrence, metastasis, survival, visual acuity and treatment complications were assessed. RESULTS: A total of 58 patients was identified: 32 patients were treated with Sr-90 and 26 with Ru-106. Mean follow-up time was 97.3 months (143.1 months after Sr-90, and 40.2 months after Ru-106). All lesions were epibulbar, the median tumour thickness was 0.9 mm. Local recurrence occurred in 13/58 cases (22%), with a 5-year recurrence rate of 21%. Local recurrence occurred equally often in both protocols, with 5-year recurrence rates of 19% (Sr-90) versus 23% (Ru-106) (p = 0.68). Metastasis developed in 3/58 cases (5%), with 2 cases after Sr-90, and 1 after Ru-106 (p = 1.00). The most reported complications were pain (29%), dry eyes (21%), symblepharon (9%), ptosis (12%) and cataract (9%). No severe corneal or scleral complications were observed. Median visual acuity was 1.00 pre-surgery, at the end of follow-up this was 1.00 (Sr-90) and 0.95 (Ru-106). CONCLUSION: Local excision with adjuvant brachytherapy provides good tumour control with excellent visual outcome and mild side effects in patients with limited conjunctival melanoma. Results after Sr-90 or Ru-106 were comparable; a choice for either treatment may be based on experience of the clinician and availability of materials.

To Study and Determine the Role of Anterior Segment Optical Coherence Tomography and Ultrasound Biomicroscopy in Corneal and Conjunctival Tumors.

Purpose. To analyze and describe corneal and conjunctival tumor thickness and internal characteristics and extension in depth and size and shape measured by two noninvasive techniques, anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM). Design. Systematic review. Methods. This systematic review is based on a comprehensive search of 4 databases (Medline, Embase, Web of Science, and Cochrane Library). Articles published between January 1, 1999, and December 31, 2015, were included. We searched for articles using the following search terms in various combinations: "optical coherence tomography", "ultrasound biomicroscopy", "corneal neoplasm", "conjunctival neoplasm", "eye", "tumor" and "anterior segment tumors". Inclusion criteria were as follows: UBM and/or AS-OCT was used; the study included corneal or conjunctival tumors; and the article was published in English, French, Dutch, or German. Results. There were 14 sources selected. Discussion. Several studies on the quality of AS-OCT and UBM show that these imaging techniques provide useful information about the internal features, extension, size, and shape of tumors. Yet there is no enough evidence on the advantages and disadvantages of UBM and AS-OCT in certain tumor types. Conclusion. More comparative studies are needed to investigate which imaging technique is most suitable for a certain tumor type.

Conjunctival melanoma in the Netherlands: a nationwide study.

PURPOSE: To evaluate risk factors for local recurrence, regional and distant metastases, and mortality associated with conjunctival melanoma. METHODS: This was a retrospective study of 194 patients with histologically confirmed conjunctival melanoma diagnosed between 1950 and 2002 in the Netherlands. Data were collected from all university centers and many nontertiary hospitals, using the National Pathology and the Leiden Oncologic Registration Systems. Based on the number of incidences, this study included 70% of the conjunctival melanomas in The Netherlands. Clinical and histopathological data for conjunctival tumors were reviewed and compared with data reported in the literature. Risk factors for local, regional, and distant metastases and survival were analyzed using the Kaplan-Meier and Cox regression analyses. RESULTS: Of 194 patients with conjunctival melanoma, 112 had a local recurrence (median, 1; range, 1-9) during follow-up (median, 6.8 years; range, 0.1-51.5). Location was the most important risk factor for development of local recurrence, and significantly more occurred with nonepibulbar (log rank, P=0.044) tumors. Significantly fewer local recurrences occurred with tumors initially treated with excision and adjuvant brachytherapy rather than with excision only (log rank, P=0.008) or with excision and cryotherapy (log rank, P <0.038). Forty-one (21%) patients had regional lymph node metastases, mostly to the parotid or preauricular lymph nodes (n=26; 13%). Risk factors for regional metastases were tumor thickness (log rank, P <0.001) and tumor diameter (log rank, P=0.010). Forty-nine (25%) patients (mean, 4.37 years) had development of distant metastases, mainly in the lung, liver, skin, and brain. Tumor-related survival was 86.3% (95% confidence interval [CI], 81.0-91.6) at 5 years, 72% (95% CI, 79.7-64.4) at 10 years, and 67% (95% CI, 58.9-76.1) at 15 years. The main mortality risk factors were nonepibulbar location (log rank, P <0.0001) and tumor thickness (log rank, P=0.0004). CONCLUSIONS: Nonepibulbar tumors more often recur locally and are associated with a shorter survival independent of other risk factors. Tumor thickness is also an important predictor of regional and distant metastases, as well as survival. A prospective study is needed to compare the effect of excision with radiotherapy and excision with cryotherapy on the number of local recurrences, exenteration rate, and survival.

Intraocular lens exchange technique for an opacified bag-in-the-lens.

We describe the intraocular lens (IOL) exchange technique that is specific to the bag-in-the-lens IOL. The subsequent IOL analysis displayed a deep granular opacification consisting predominantly of calcium and phosphates that has been described in hydrophilic IOLs.

Distribution of GNAQ and GNA11 Mutation Signatures in Uveal Melanoma Points to a Light Dependent Mutation Mechanism.

Uveal melanomas (UM) originate from melanocytes in the interior wall of the eye, namely from the iris, ciliary body and the choroid with marked differences in light exposure (from dark anterior to illuminated posterior). In contrast to UV radiation, focused or converging visible light readily reaches the retina and can damage DNA which possibly contributes to UM development. In this report choroidal, ciliochoroidal and iridociliary melanomas were analyzed for GNAQ and GNA11 mutations which were subsequently correlated to the location of tumor origin. Hotspot mutations in GNAQ and GNA11 can be divided in A>T and in A>C mutation signatures. The GNAQ A626C mutation (Q209P) was almost exclusively observed in choroidal melanomas from the illuminated posterior side. On the other hand, ciliochoroidal UM from the dark anterior side with mostly A>T mutations were clearly associated with light-colored eyes. Combined these data suggest a light and a pigment dependent etiology in UM development.

Ruthenium plaque radiation therapy for iris and iridociliary melanomas.

PURPOSE: To determine the long-term effects of ruthenium-106 plaque radiation therapy for iris and iridociliary melanomas in terms of tumour regression and complications. METHODS: Between 1 November 1997 and 31 December 2007, 36 patients with an iris or iridociliary melanoma were treated with Ruthenium-106 (Ru-106) ophthalmic plaque radiation therapy. The median follow-up was 6.5 years with a range of 2-11 years. The mean tumour apex dose was 151.5 Gy. Main outcome measures were local tumour control and radiation-related ocular complications. RESULTS: The mean age of the patients at the time of treatment was 54 years (range 14-82). The tumours had a median largest basal dimension of 4.8 mm (range 3-11) and a prominence of 2.3 mm (range 0.8-5), with a median involvement of three clock hours (range 1-6). The tumours were confined to the iris in 14 patients (39%), extended into the anterior ciliary body in 12 (33%), while the anterior ciliary body tumour extended into the iris in ten patients (28%). Tumours regressed in all patients (100%) with a mean regression of 80% of the original tumour size at 7 years of follow-up. Radiation-related complications included corneal erosions on the first postoperative day in nine patients (25%), cataract in four of 11 patients free of cataract before treatment (36%) and postradiation glaucoma in one patient (3%). Visual acuity of 20/200 or worse was present in one of 20 patients (5%) at 6 years of follow-up. Local recurrences occurred in two patients (5%), 2 and 5 years after the radiation therapy respectively, and both underwent enucleation. Distant metastases occurred in one of these enucleated patients (3%) 2 years after treatment. CONCLUSION: Ru-106 plaque radiation therapy for iris and iridociliary melanoma resulted in good local tumour control and preservation of visual acuity with few and treatable side-effects.

Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study.

OBJECTIVE: To collaborate with multiple centers to identify representative epidemiological, clinical, and pathologic characteristics of melanoma of the iris. This international, multicenter, Internet-assisted study in ophthalmic oncology demonstrates the collaboration among eye cancer specialists to stage and describe the clinical and pathologic characteristics of biopsy-proven melanoma of the iris. METHODS: A computer program was created to allow for Internet-assisted multicenter, privacy-protected, online data entry. Eight eye cancer centers in 6 countries performed retrospective chart reviews. Statistical analysis included patient and tumor characteristics, ocular and angle abnormalities, management, histopathology, and outcomes. RESULTS: A total of 131 patients with iris melanoma (mean age, 64 years [range, 20-100 years]) were found to have blue-gray (62.2%), green-hazel (29.1%), or brown (8.7%) irides. Iris melanoma color was brown (65.6%), amelanotic (9.9%), and multicolored (6.9%). A mean of 2.5 clock hours of iris was visibly involved with melanoma, typically centered at the 6-o'clock meridian. Presentations included iritis, glaucoma, hyphema, and sector cataract. High-frequency ultrasonography revealed a largest mean tumor diameter of 4.9 mm, a mean maximum tumor thickness of 1.9 mm, angle blunting (52%), iris root disinsertion (9%), and posterior iris pigment epithelium displacement (9%). Using the American Joint Commission on Cancer-International Union Against Cancer classification, we identified 56% of tumors as T1, 34% of tumors as T2, 2% of tumors as T3, and 1% of tumors as T4. Histopathologic grades were G1-spindle (54%), G2-mixed (28%), G3-epithelioid (5%), and undetermined (13%) cell types. Primary treatment involved radiation (26%) and surgery (64%). Kaplan-Meier analysis found a 10.7% risk of metastatic melanoma at 5 years. CONCLUSIONS: Iris melanomas were most likely to be brown and found in the inferior quadrants of patients with light irides. Typically small and unifocal, melanomas are commonly associated with angle blunting and spindle cell histopathology. This multicenter, Internet-based, international study successfully pooled data and extracted information on biopsy-proven melanoma of the iris.

Anterior segment imaging for iris melanocytic tumors.

PURPOSE: To determine the role of anterior segment optical coherence tomography (AS-OCT) and other anterior segment imaging techniques (Pentacam, slit-lamp optical coherence tomography [SL-OCT]) for analysis of iris melanocytic tumors and to compare results with clinical features and ultrasound biomicroscopy (UBM). METHODS: Between 2006 and 2009, 61 patients with melanocytic iris tumors were examined using different anterior segment imaging techniques: Pentacam, SL-OCT, AS-OCT, and UBM (50 MHz). Pentacam was performed in 17 patients, SL-OCT in 12, AS-OCT in 46, and UBM in 49. RESULTS: The Pentacam images identified the tumor in 3 of 17 patients (18%), SL-OCT in 8 of 12 (67%), and AS-OCT in 44 of 46 (96%). Anterior segment optical coherence tomography results were compared with UBM in 42 patients: in 86% the results were comparable, although AS-OCT visualized a ciliary body extension of iris tumors only in 1 out of 3 cases analyzed. CONCLUSIONS: Iris melanocytic tumors were located by AS-OCT in 96% of cases and results were comparable to UBM imaging, while both SL-OCT and Pentacam are less reliable for detecting and measuring anterior segment lesions. Anterior segment optical coherence tomography gives precise anterior eye segment diameters, which are useful for the brachytherapy dosage calculation module developed at the Leiden University Medical Center. Therefore, AS-OCT is a reliable, convenient, and noncontact method for detecting and measuring pure iris tumors, but UBM is superior in detecting a ciliary body extension of these tumors.

Predictive value of exfoliative cytology in pigmented conjunctival lesions.

PURPOSE: Pigmented lesions of the conjunctiva are often difficult to classify clinically. Exfoliative cytology may be helpful, but reliable data regarding the sensitivity and specificity of this test are currently lacking. We determined the value of exfoliative cytology with regard to pigmented conjunctival lesions. METHODS: A total of 294 smears from 182 patients were screened for malignancy within 6 months of exfoliative cytology. Smears were classified according to the following categories: grade 0 = insufficient material for diagnosis; grade 1 = normal conjunctival cells; grade 2 = melanocytes with mild atypia; grade 3 = melanocytes with moderate atypia, and grade 4 = melanocytes with severe atypia. RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of exfoliative cytology were 85%, 78%, 59% and 93%, respectively. CONCLUSION: Exfoliative cytology is a fast, easy and non-invasive technique that may be used in the evaluation of patients with a pigmented conjunctival lesion.

Maintenance of immune tolerance depends on normal tissue homeostasis.

Ags expressed at immune privileged sites and other peripheral tissues are able to induce T cell tolerance. In this study, we analyzed whether tolerance toward an intraocular tumor expressing a highly immunogenic CTL epitope is maintained, broken, or reverted into immunity in the event the anatomical integrity of the eye is lost. Inoculation of tumor cells into the anterior chamber of the eye of naive B6 mice leads to progressive intraocular tumor growth, an abortive form of CTL activation in the tumor-draining submandibular lymph node, and systemic tolerance as evidenced by the inability of these mice to reject an otherwise benign tumor cell inoculum. Loss of anatomical integrity of the eye as a consequence of phthisis resulted in loss of systemic tolerance and the emergence of effective antitumor immunity against an otherwise lethal tumor challenge. Phthisis was accompanied by dendritic cell maturation and preceded the induction of systemic tumor-specific CTL immunity. Our data show that normal tissue homeostasis and anatomical integrity is required for the maintenance of ocular tolerance and prevention of CTL-mediated immunity. These data also indicate that tissue injury in the absence of viral or microbial infection can act as a switch for the induction of CTL immunity.