Eyelids metastases from uveal melanoma: clinical and histopathologic features of two cases and literature review.

PURPOSE: To report the clinical and histopathologic features of two cases of eyelids metastases from uveal melanoma diagnosed in a metachronous and synchronous fashion. METHODS: Monocentric retrospective case series of histopathologically proven eyelids metastases from uveal melanoma at our institution. RESULTS: Two patients were presented to our hospital for upper eyelids pigmented and firm lesions. Patient 1 had an history of left uveal melanoma treated conservatively with proton beam therapy 5 years earlier. Examination revealed bilateral upper eyelids lesions. Patient 2 had no malignancy history but was incidentally diagnosed with a cerebral nodule few months earlier. Examination revealed a right upper eyelid nodule and a previously unknown right uveal melanoma. Excisional biopsy was performed for both patients. Pathological assessment allowed the presence of melanoma cells. The lack of BAP1 nuclear expression on immunohistochemistry as well as the absence of cutaneous or mucosal melanoma were consistent with an uveal origin. Diffuse metastatic spread was noted for both patients. Systemic therapies were prescribed. Patient 1 died from metastatic spread (62 months and 4 months after uveal melanoma diagnosis and eyelids metastases removal, respectively) whereas patient 2 was still alive (14 months follow up). CONCLUSIONS: Eyelids metastases from uveal melanoma is an exceptional finding. Excisional biopsy and pathological assessment are of main importance to confirm the diagnosis and to identify genetic mutations for further targeted therapies. Currently, prognosis remains poor.

Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy.

The aim was to investigate the levels of cytokines and soluble IL-6R in the tears of patients with thyroid-associated orbitopathy (TAO) disease. Schirmer's test was adopted to collect tears from TAO patients (N = 20, 17 women, mean age (±SD): 46.0 years (±13.4)) and healthy subjects (N = 18, 10 women, 45.4 years (±18.7)). Lacrimal cytokines and soluble IL-6R (sIL-6R) were measured using a 10-plex panel (Meso Scale Discovery Company) and Invitrogen Human sIL-6R Elisa kit, respectively. Tear levels of IL-10, IL-12p70, IL-13, IL-6 and TNF-α appeared significantly higher in TAO patients than in healthy subjects. Interestingly, IL-10, IL-12p70 and IL-8 levels increased in tears whatever the form of TAO whereas IL-13, IL-6 and TNF-α levels were significantly elevated in inflammatory TAO patients, meaning with a clinical score activity (CAS) ≥ 3, compared to controls. Furthermore, only 3 cytokines were strongly positively correlated with CAS (IL-13 Spearman coeff. r: 0.703, p = 0.0005; IL-6 r: 0.553, p = 0.011; IL-8 r: 0.618, p = 0.004, respectively). Finally, tobacco use disturbed the levels of several cytokines, especially in patient suffering of TAO. The differential profile of lacrimal cytokines could be useful for the diagnosis of TAO patients. Nevertheless, the tobacco use of these patients should be taken into account in the interpretation of the cytokine levels.

Thyroid-Associated Orbitopathy and Biomarkers: Where We Are and What We Can Hope for the Future.

BACKGROUND: Thyroid-associated orbitopathy (TAO) is the most common autoimmune disease of the orbit. It occurs more often in patients presenting with hyperthyroidism, characteristic of Graves' disease, but may be associated with hypothyroidism or euthyroidism. The diagnosis of TAO is based on clinical orbital features, radiological criteria, and the potential association with thyroid disease. To date, there is no specific marker of the orbital disease, making the early diagnosis difficult, especially if the orbital involvement precedes the thyroid dysfunction. SUMMARY: The goal of this review is to present the disease and combine the available data in the literature concerning investigation of TAO biomarkers. CONCLUSIONS: Despite the progress done in the understanding of TAO disease, some important pieces are still missing. Typically, for the future, major efforts have to be done in the discovery of new biomarkers, validation of the suspected candidates on multicenter cohorts with standardized methodologies, and establishment of their clinical performances on the specific clinical application fields in order to improve not only the management of the TAO patients but also the therapeutic options and follow-up.

Thyroid-associated orbitopathy and tears: A proteomics study.

To date, Thyroid-Associated Orbitopathy (TAO), an autoimmune inflammatory disease affecting the eye, remains poorly characterised and its diagnosis challenging. The aim of this study was to investigate the tears of the TAO patients in order to identify potential biomarkers. Two independent quantitative Tandem Mass Tag™ 6-plex experiments were done. After in-solution digestion and isoelectric fractionation, the 12 fractions were analysed with a LTQ Orbitrap Velos coupled to a liquid chromatography. Raw files were searched against Swiss-Prot-AC database using Proteome Discoverer software, with a false discovery rate of 1% at peptide and protein levels. The differential proteins were then verified using orthogonal approaches in independent patients. Globally, 712 tear proteins were quantified with 2 unique peptides. Interestingly, cystatin c (TAO/controls ratio: 1.53), alpha-1 antichymotrypsin (ratio: 1.70) and retinal dehydrogenase (ratio: 0.68), displaying differential levels in the tears of TAO patients using proteomics experiments emerged as highly promising biomarkers after verification. In conclusion, this proteomics study supports the idea that tears reflect biological modifications occurring in a disease context and can therefore be a promising fluid for biomarker discovery. Moreover, our study identified three candidates that could in the future open new avenues in the diagnosis of TAO disease. SIGNIFICANCE: Thyroid associated orbitopathy (TAO) is the most common disease affecting the orbit. Moreover, the later, severe stages of the disease can be sight threating [1]. On the other hand, the early sign and symptoms can be mistaken with other ocular pathologies [2]. Here we explore the modification of the tear content of the TAO patients using proteomics strategies and we proposed three new biomarker candidates, which could allow the early diagnosis of the disease and prompt action to prevent more severe stages. Moreover, our findings could also help to better understand the pathophysiology of the disease.

Ocular adnexal (orbital) solitary fibrous tumor: nuclear STAT6 expression and literature review.

PURPOSE: To report the clinico-pathological features of solitary fibrous tumor occurring in the ocular adnexa (OA) in a single center. To assess the presence of NAB2-STAT6 genes fusion in OA solitary fibrous tumor detected by nuclear overexpression of STAT6. METHODS: Retrospective study including orbital and OA solitary fibrous tumors treated between 2006 and 2014 in our center. The clinical, radiological, and histopathological findings were evaluated. STAT6 expression was assessed by immunohistochemistry. RESULTS: Five patients were identified and presented with a chronic OA mass. The tumors were radiologically well delimited, highly vascularized and without bone erosion. All the patients underwent complete surgical excision. Pathological examination confirmed solitary fibrous tumor in all cases. All tumors demonstrated a nuclear expression of STAT6. There were no recurrences, with a mean follow-up of 5 years after surgery. Our review demonstrated that proptosis was the most common presentation occurring in 60 % of the cases. In the ocular adnexa, adverse histological criteria were found in 19.7 % of the tumors, and recurrences were observed in 48 % of these cases. Thirty-six percent of patients presented at least one local recurrence, and metastastic spread was found in 2.4 % of the cases. Tumor-related death was described in two cases. CONCLUSION: Ocular adnexal SFT are rare and usually present as a chronic orbital mass with proptosis. In the OA, solitary fibrous tumor demonstrates STAT6 nuclear expression, as documented in other locations. Recurrences are unusual and metastasis exceptional. Initial surgical resection should be complete in order to avoid recurrence.