Mutations in MC4R facilitate the angiogenic activity in patients with orbital venous malformation.

IMPACT STATEMENT: The detailed molecular mechanism of orbital venous malformation (OVM) is still not clear. Using whole exome sequencing, 4 types of melanocortin 4 receptor (MC4R) mutation were detected in 7 of 27 patients with OVM, and all types of MC4R mutations resulted in the upregulation of MC4R expression. In vitro study indicated that MC4R has impacts on the proliferation, cell cycle, migration, and tube formation of the endothelial cells. Moreover, MC4R mutations altered the downstream signaling, including cAMP concentration and the expression levels of several PI3K/AKT/mTOR downstream genes, including p21, cyclin B1, ITGA10, and ITGA11. MC4R mutations may lead to the pathogenesis of OVM through modulating the downstream signaling to alter the angiogenic activity of endothelial cells.

Poly (ADP-ribose) polymerase-1 (PARP-1) in Chinese patients with Graves' disease and Graves' ophthalmopathy.

We aimed to evaluate the genetic variation of poly (ADP-ribose) polymerase-1 (PARP-1) as risk factor in development of Graves' disease (GD) and Graves' ophthalmopathy (GO) among Chinese individuals. Patients with confirmed diagnosis of GD or healthy individuals with no clinical symptoms of hyperthyroiditis were enrolled at the Department of Ophthalmology, Tianjin First Center Hospital, China. Genetic polymorphism was studied in plasma DNA samples of subjects by polymerase chain reaction of restriction fragment length polymorphism to confirm our hypothesis. Cytokine levels were measured routinely on serum samples of subjects by sandwich ELISA technique. Patients with GG genotype (odds ratio (OR) 95% CI = 2.25 (1.35-3.73), p = 0.002) and carriers of G allele (OR = 2.03 (1.23-3.36), p = 0.006) were at high risk of developing ophthalmopathy. Polymorphism of del/ins of nuclear factor-κB1 gene (NFkB1) gene (OR = 7.1 (2.88-17.52), p < 0.0001) and PARP-1 C410T polymorphism was found to be associated with GO (p < 0.05). Cytokine level was significantly higher in patients with GD (p < 0.05), but no significant change in cytokines level among GO patients from baseline (p > 0.05). Our study results recommended that polymorphism of PARP-1 gene is more likely responsible for development of GD in Chinese individuals. We also observed that the polymorphism of gene-related del/ins to NFkB1 in development of GO.

[The clinical analysis of cranio-orbital communicating tumors].

OBJECTIVE: To investigate the clinical manifestations, imageological features, surgical approaches and prognosis of cranio-orbital communicating tumors. METHODS: The retrospective analysis was performed in the 22 patients of cranio-orbital communicating tumors in the past three years. CT and MRI examinations were applied in all cases. Of 16 patients were treated by surgical approaches, Of 6 patients were for radiation therapy. RESULTS: Of 22 cases, 2 cases were osteoid osteoma, 3 cases were meningioma, 1 case was aneurysmal bone cyst, 2 cases were mucous cyst, 2 cases were schwannoma, 2 cases were adenoid cystic carcinoma of lacrimal gland, 2 cases were metastatic carcinoma, and 2 cases were rhabdomyosarcoma. Other 6 cases were treated by radiotherapy without pathological diagnosis. 8 cases for orbital operation including excision of orbital contents 1/8, anterior orbitotomy 3/8, and lateral orbitotomy 4/8, and 8 cases for transcranial operation including frontotemporal orbital roof approach 3/8 and pterion approach 5/8. After operation, the vision acuity of 3 cases was improved, of 10 cases was unchanged and of 3 cases was decreased. Two patients died of metastasis. Among 8 cases of transcranial operation, the complaints such as eye movement disorder, proptosis and conjunctival edema emerged in 1 case. However, among 8 cases of orbital operation, such above complaints were respectively found in 7, 5 and 6 cases. CONCLUSIONS: CT and MRI have the great value for diagnosis of cranio-orbital communicating tumors, especially combined with enhanced contrast MRI. Resection of cranio-orbital communicating tumors via the transcranial surgical approach is the effective surgical approach for cranio-orbital communicating tumors.

[Imaging feature and clinical histological analysis of 12 adenoid cystic carcinoma of the lacrimal gland].

OBJECTIVE: To study the imaging and histologic features of adenoid cystic carcinoma (ACC) of the lacrimal gland. METHODS: It was a retrospective case series study. Twelve patients with ACC of the lacrimal gland were surgically treated in Tianjin First Center Hospital from September 2009 to November 2011. The 5 men and 7 women aged from 22 to 63 years (average 42.6 years). The imaging and histologic features of 12 cases with ACC of the lacrimal gland pathologically confirmed were retrospectively reviewed. Twelve cases were performed with CT scan, 10 cases with MRI scan. All patients were followed up by telephone and reexamination in the outpatient service, and 2 patients were lost to follow-up. RESULTS: The lesions originated in the orbital lobe of the lacrimal gland. The most common presenting symptom was pain; it was followed by proptosis, ptosis, decreased visual acuity and diplopia. The 7th Edition of the American Joint Committee on Cancer TNM Classification system for Lacrimal Gland Tumors stages were as follows: T1N0M0 1 patients, T2N0M0 4 patients, T4N0M0 7 patients. Preoperative CT imaging suggested that bony involvement of the lacrimal gland fossa in 7 patients;this was histologically confirmed in 6 of the 7. Preoperative CT imaging suggested no bone involvement in 5 patients, 1 of whom had bone involvement by histology. The positive rate of CT scan was 6/7. Preoperative MRI imaging suggested that bony involvement of the lacrimal gland fossa in 7 patients;this was histologically confirmed in 6 of the 7. Preoperative MRI imaging suggested no bone involvement in 3 patients who were confirmed by histology. The positive rate of MRI scan was 6/7. Overall, 7 of 12 histologically evaluable cases had bone invasion. Five of the histologically proven 7 patients with bone involvement had a predominantly basaloid pattern, 2 mixed pattern. Three patients had local recurrence. CONCLUSIONS: The imaging for ACC of the lacrimal gland is characteristic. ACC of the lacrimal gland is associated with the high rate of bone invasion. The basaloid variety has more aggressive biologic behavior. The risk of local recurrence may be associated with the histologic types and stages of lacrimal gland adenoid cystic carcinoma.

[Analysis of treatment and prognosis of orbital adenoid cystic carcinoma].

OBJECTIVE: To summarize the treatment outcomes of orbital adenoid cystic carcinoma and to evaluate prognostic factors. METHOD: A retrospective case series study was performed on 75 patients with orbital adenoid cystic carcinoma treated from 1991 to 2006. RESULTS: The 2- and 5-year local recurrence rate of solid type orbital adenoid cystic carcinoma was significantly higher than that of the adeno-tubiform type [2-year, 85% (17/20) vs 23.53% (8/34), chi(2) = 19.14, P = 0.000; 5-year, 100% (19/19) vs 64.52% (20/31), Fisher's exact test, P = 0.003]. The regional extension and distant metastasis of solid type were more than those of adeno-tubiform type. The 5-year local recurrence rate treated by postoperative radiation was lower than that treated with only surgical excision [70% (14/20) vs 92.86% (13/14); Fisher's exact test, P = 0.198]. The 5-year local recurrence rate in patients initially treated by orbital evisceration during the first time was lower than that of cases which evisceration procedure was used after the recurrence [25% (1/4) vs 75% (6/8), Fisher's exact test, P = 0.222]. Tumors may extend into intracalvarium, nasal cavity and temporal fossa. They may spread to the lung, bone, liver and lymph node. The 5-year metastasis rate was 25.71% (9/35). Both of the lung and bone metastasis rates were 33.33% (3/9). The overall 5-year accumulative survival was 74.29% (26/35), mortality was 25.71% (9/35), and rate of survival without tumor recurrence was 37.14% (13/35). The 10-year disease free survival rate was 17.14% (6/35). Patients were most likely to die with intracranial extension. Surgical excision with postoperative radiation improved the 5-year survival rate to 80% (16/20). CONCLUSIONS: Orbital adenoid cystic carcinoma is one of the most malignant tumors in the orbit. They have a high local recurrence rate and survival rate. Tumor histological types and the treatment procedure can influence the prognosis. Combined therapy may decrease the recurrence and increase the survival rate.

[Clinical features and therapy of benign lymphoepithelial lesion].

OBJECTIVE: To report the clinical features of benign lymphoepithelial lesion and to further characterize recommendations for its therapy strategy. METHODS: It was a retrospective case sires. Retrospective analyze the clinical characteristics, imaging features, pathological manifestation and the treatment effect from the clinical materials of 9 cases of patients with benign lymphoepithelial lesion presenting to Tianjin Eye Hospital from Jan 2006 to Dec 2007. RESULTS: The 9 cases, in which 7 cases were female, 7 cases had lesions on both eyes, demonstrated unpainful swelling of the lacrimal glands and in different degree of salivary glands or had history of tumor resection of salivary glands. Orbital CT scanning showed increased homogeneous density with clear boundary in the lacrimal gland area. Color doppler ultrasonography displayed elliptical space occupying with clear boundary and homogeneous internal echos of the lacrimal gland area. Six patients received treatment with large dose of glucocorticoid for 1 - 2 courses, and the symptoms and signs were significantly alleviated. Three patients were operated to excise the lacrimal gland masses due to imperfect treatment effect of medication or in order to make definite diagnosis. The postoperative pathological results supported the diagnosis of benign lymphoepithelial lesion. No recurrence happened in the follow-up. CONCLUSIONS: A clinical condition with swelling of either or both lacrimal gland and of any salivary gland, and accompanied with systemic relative diseases should be considered benign lymphoepithelial lesion. Imaging examinations are helpful to definite diagnosis. Most patients are sensitive to the glucocorticoid treatment. The dose of glucocorticoid should be large at the beginning of treatment. Surgical excision can be applied to the cases insensitive to medications or difficult to be diagnosed. The definite diagnosis should be made through pathological examinations.