MR Imaging Characteristics of Solitary Fibrous Tumors of the Orbit : Case Series of 18 Patients.

PURPOSE: Solitary fibrous tumor (SFT) of the orbit is a rare tumor that was first described in 1994. We aimed to investigate its imaging characteristics that may facilitate the differential diagnosis between SFT and other types of orbital tumors. MATERIAL AND METHODS: Magnetic resonance imaging (MRI) data of patients with immunohistochemically confirmed orbital SFT from 2002 to 2022 at a tertiary care center were retrospectively analyzed. Tumor location, size, morphological characteristics, and contrast enhancement features were evaluated. RESULTS: Of the 18 eligible patients 10 were female (56%) with a mean age of 52 years. Most of the SFTs were oval-shaped (67%) with a sharp margin (83%). The most frequent locations were the laterocranial quadrant (44%), the extraconal space (67%) and the dorsal half of the orbit (67%). A flow void phenomenon was observed in nearly all cases (94%). On the T1-weighted imaging, tumor signal intensity (SI) was significantly lower than that of the retrobulbar fat and appeared predominantly equivalent (82%) to the temporomesial brain cortex, while on T2-weighted imaging its SI remained equivalent (50%) or slightly hyperintense to that of brain cortex. More than half of the lesions showed a homogeneous contrast enhancement pattern with a median SI increase of 2.2-fold compared to baseline precontrast imaging. CONCLUSION: The SFT represents a rare orbital tumor with several characteristic imaging features. It was mostly oval-shaped with a sharp margin and frequently localized in the extraconal space and dorsal half of the orbit. Flow voids indicating hypervascularization were the most common findings.

Reconstruction of Orbital Exenteration Defects with Cross-median Forehead Flaps.

The aim of this study was to examine the role of forehead flaps in the reconstruction of orbital defects after exenteration. Patients undergoing orbital exenteration and reconstruction using median forehead flaps from January 2002 to August 2019 were enrolled in this retrospective study. All the patients were evaluated for wound complications, functional results, and tumor relapse. In total, 105 patients completed the study. Twenty-nine complications in 24 of these patients were assessed. The most common complications were wound dehiscence (11%), partial necrosis of the flap (6%), and bleeding (4%). A major complication occurred in two patients (2%), necessitating surgical correction. Only one patient had a local relapse. Sixty patients received osseointegrated implants, and 58 of them were treated with facial prostheses. The follow-up periods ranged from 6 to 189 months. Thus, forehead flap reconstruction after exenteration is a reliable method with a low complication rate. This technique can be used for primary or secondary reconstruction, and excellent long-term functional results can be achieved. A relapse-oriented follow-up is certainly possible.

Solitary Fibrous Tumours of the Orbit - Clinical Pathology, Therapy and Prognosis. / Solitär fibröse Tumoren der Orbita ­ klinisch-pathologische Charakteristik, Therapie und Prognose.

BACKGROUND: Solitary fibrous tumours are rare. The aim of this study is to describe the clinical features, therapy and outcome of affected patients and to identify factors associated with recurrence. METHODS: Retrospective study of a cohort of 20 patients who underwent surgery for orbital solitary fibrous tumour at the University Department of Oral and Maxillofacial Surgery between 2002 and 2023. Demographic, clinical, and therapeutic data as well as tumour follow-up results were collected. Tumour volume and molecular genetic mutations were retrospectively determined. RESULTS: The median patient age was 49.5 years at initial surgery. The left orbit was affected in 65% of cases. The most common clinical symptom was proptosis (80%). This was reported with a mean lateral difference of 3.9 mm (range: 1 - 10 mm). The tumours were localised predominantly in the intra- and extraconal space, craniolateral quadrant and middle third. The median tumour volume was 7.66 cm³ (range 2.15 - 12.57 cm³). In all patients, the diagnosis was made by pathological examination. All tumours investigated showed a NAB2-STAT6 mutation. The most frequently detected mutation was the fusion NAB2 exon 4 - STAT6 exon 2. All patients were initially managed with frontolateral orbitotomy. Incomplete resection (R1-status) occurred in 35% (n = 7). The recurrence rate was 25% (n = 5), with a median disease-free interval of 45.5 months (range 23 - 130). 80% (n = 4) of recurrences were initially R1-resected. CONCLUSION: Orbital solitary fibrous tumours are rare tumours and are clinically manifested by signs of displacement of orbital structures. Diagnosis is made by histology and immunohistochemistry and can be proven with the molecular genetic detection of the NAB2-STAT6 mutation. The therapy of choice is complete surgical resection. R1-resection is more likely in the intraconal location as well as in location in the posterior third of the orbit - due to difficult surgical accessibility. The greatest risk factor for the development of recurrence is incomplete surgical excision. Late recurrences are possible, which is why a long-term connection to a specialised clinic is necessary.

Midterm results of conjunctival reconstruction with buccal mucosa and amniotic membrane after resecting ocular surface squamous neoplasia of the fornix.

OBJECTIVE: To evaluate the midterm results of tumour resection with or without adjunctive therapy for ocular surface squamous neoplasia of the fornix, including conjunctival reconstruction with buccal mucosa and amniotic membrane. METHODS: A retrospective case-series analysis including slit-lamp examination, photographic documentation, and biopsy results (repeated when clinical findings changed). Analysis centred on eye function, complications, additional procedures, and recurrence rate. Surgical technique included tumour resection and subsequent reconstruction of lost conjunctiva with buccal mucosa and amniotic membrane. RESULTS: We included 83 affected eyes from 76 patients (mean age, 63.10 ± 14.45 years; 34 females) seen over a mean follow-up period of 26.56 ± 21.17 months. We achieved bulbus oculi salvage in 82 eyes (98.79%) and typically preserved visual acuity (mean 0.2 ± 0.5 logMAR and 0.3 ± 0.5 logMAR at presentation and last follow-up, respectively). Moreover, only 23 patients (27.71%) required corrective surgery for clinically relevant complications. The main complications included symblepharon (9.64%; n = 8), cicatricial ectropion (9.64%; n = 8), pannus (9.64%; n = 8), and corneal decompensation (8.43%; n = 7). Local tumour recurrence was seen in 23 patients (27.71%). CONCLUSIONS: These midterm results confirm the efficacy of conjunctival reconstruction with amniotic membrane and buccal mucosa after resection of ocular surface squamous neoplasia from the fornix with palpebral and bulbar conjunctiva involvement. We not only achieved good tumour control and organ salvage with high levels of organ preservation but we also achieved good functional outcomes and acceptable recurrence rates. All clinically significant complications could be corrected in separate procedures.

Novel Insights into Pathophysiology of Orbital Inflammatory Diseases and Progression to Orbital Lymphoma by Pathway Enrichment Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are currently treated with non-specific immunosuppressive agents based on non-randomized, uncontrolled studies. Therefore, relapses and prolongated courses are common and remain challenging. For a more specific therapy, a better understanding of the underlying pathophysiology is crucial. Therefore, we aimed to analyze signaling pathways to expand the knowledge on the pathophysiology and possibly identify specific targets in the future, as occurred recently in Graves' orbitopathy with the IGF-1 receptor. Furthermore, we analyzed potential mechanisms for the described potential progression to orbital MALT (mucosa-associated lymphoid tissue) lymphoma. The investigation cohort for this screening study comprised of 12 patients with either typical NSOI (n = 6), IgG4-ROD or MALT lymphoma (n = 3 each). Mean age was 56.4 ± 17 years. MALT samples, in contrast with IgG4-ROD and NSOI, showed overall upregulation for extracellular matrix receptor interaction (ECM) and adipocytokine signaling. Investigating signaling compounds for MALT samples, differentially expressed genes were re-identified as targets with relevant expression. Even though pathway analysis showed differentially altered products when comparing IgG4-ROD with MALT, main conductors of differentiation in B- and T-cell signaling were commonly altered when observing the microenvironment of examined tissues. Our data reveal the characteristic differences and similarities in genetic-expression-based pathway profiles between MALT lymphoma, IgG4-ROD and NSOI, which may be useful for elucidating the associated pathogenic mechanisms and developing specific treatments for these orbital diseases.

Evaluation of Orbital Lymphoproliferative and Inflammatory Disorders by Gene Expression Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000−2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.

Orbital aspergillosis: a case report and review of the literature.

BACKGROUND: Orbital aspergillosis is a rare sight- and life-threatening fungal infection affecting immunocompromised or otherwise healthy patients. It is often misdiagnosed due to its unspecific clinical and radiologic appearance. Therapeutic delay can have dramatic consequences. However, progress in microbiological diagnostic techniques and therapeutic experience from case series help improve the management of this disease. CASE PRESENTATION: A 78-year-old immunocompetent woman presented at an eye clinic for subacute swelling, reddening, and ptosis of her left upper eyelid. Based on radiologic and histologic considerations, she was treated for idiopathic orbital inflammation, but her condition worsened. After a second biopsy of the orbital mass, aspergillosis was diagnosed. Her condition improved promptly after initiation of an oral voriconazole treatment. Additionally, using a polymerase chain reaction (PCR) assay, A. fumigatus was identified on tissue of both biopsies and its azole susceptibility was examined simultaneously. CONCLUSIONS: In the case described here, oral antifungal treatment was sufficient for the therapy of invasive orbital aspergillosis. Performing fungal PCR on orbital tissue can accelerate the diagnostic process and should be performed in ambiguous cases of slowly growing orbital mass. Finally, interdisciplinary management is the key to optimal treatment of orbital tumours and infections.

Periorbital, conjunctival and primary intraorbital carcinomas: Survival and risk factors after orbital exenteration.

OBJECTIVES: This study aimed to analyse the disease-free survival (DFS), overall survival (OS) and risk factors after orbital exenteration in patients with periorbital, conjunctival and primary intraorbital carcinomas. METHODS: Patients undergoing orbital exenteration due to a primary carcinoma between March 2000 and March 2018 were included in this retrospective study. Risk factors in all the patients were evaluated using univariate and multivariate analyses. RESULTS: In total, 97 patients were enroled in this study. The most common tumours were conjunctival carcinoma (35 cases), squamous cell carcinoma of the skin (27 cases) and basal cell carcinoma (20 cases). The median follow-up period was 36 months. The average age of the patients was 67.3 years (range, 29-93 years). In all the patients, OS was 85% after 1 year and 69% after 5 years, while DFS was 71% after 1 year and 55% after 5 years. Univariate analysis of OS revealed that the following parameters were predictive of a poor prognosis: localisation, neck dissection, lymph node metastases, lymphatic invasion, perineural invasion, resection margins and immunosuppression. Multivariate analysis revealed resection margins as the only independent risk factor. CONCLUSION: Orbital exenteration is rarely necessary in patients with periorbital, conjunctival and primary intraorbital carcinomas; however, it can be performed as an ultima ratio treatment with a curative intent. Clear margins can be achieved in most cases. OS and DFS are not significantly different in the subgroups. In most cases, recurrence occurs within the first 2 years.

Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing.

The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is not fully understood. We performed whole genome sequencing (WGS) and/or whole exome sequencing (WES) for 13 cases of OAML and sequenced 38 genes selected from this analysis in a large cohort of 82 OAML. Besides confirmation of frequent mutations in the genes transducin beta like 1 X-linked receptor 1 (TBL1XR1) and cAMP response element binding protein (CREBBP), we newly identifed JAK3 as a frequently mutated gene in OAML (11% of cases). In our retrospective cohort, JAK3 mutant cases had a shorter progression-free survival compared with unmutated cases. Other newly identified genes recurrently mutated in 5-10% of cases included members of the collagen family (collagen type XII alpha 1/2 (COL12A1, COL1A2)) and DOCK8. Evaluation of the WGS data of six OAML did not reveal translocations or a current infection of the lymphoma cells by viruses. Evaluation of the WGS data for copy number aberrations confirmed frequent loss of TNFAIP3, and revealed recurrent gains of the NOTCH target HES4, and of members of the CEBP transcription factor family. Overall, we identified several novel genes recurrently affected by point mutations or copy number alterations, but our study also indicated that the landscape of frequently (>10% of cases) mutated protein-coding genes in OAML is now largely known.

Autologous dermis - Fat grafts as primary and secondary orbital transplants before rehabilitation with artificial eyes.

OBJECTIVE: The aim of this study was to examine the role of autologous dermis-fat grafts in the reconstruction of orbital soft-tissue defects. PATIENTS: Thirty-six patients (3-84 years) were enrolled in this retrospective study from 2002 to 2014. The dermis-fat graft was primarily transplanted in seven cases, and secondarily in 29 patients. All the patients were evaluated for complications, adequate prosthetic cavity, possibility of artificial eye supply and movement, as well as cosmetic results. Follow-up periods ranged from 25 to 144 months. RESULTS: All the patients could be supplied with an artificial eye in the long term after dermis-fat transplantation. The clinical evaluation revealed 17 complications allocated to 11 patients. A major complication occurred in three patients (8.3%) so that a surgical correction was necessary. Thirty-three patients (91.7%) showed an aesthetically stable long-term outcome. CONCLUSION: Dermis-fat grafts for reconstruction of anophthalmic orbit represent a reliable method with a low complication rate and good cosmetic and functional results. The graft can be used as primary and secondary transplants. The stable long-term results and high aesthetic satisfaction lead us to recommend this method as a routine operation.

Correction of whistle deformity using autologous free fat grafting: first results of a pilot study and review of the literature.

PURPOSE: Whistle deformities are frequent sequelae after surgical correction of cleft lip, trauma, or tumor excision. The aim of this study was to examine the role of autologous free fat grafting in the reconstruction of whistle deformity. PATIENTS: Fifteen patients with whistle deformity were enrolled in this pilot study. The mean follow-up period was 19 months. Liposuction was done followed by the replantation of an average of 2.2 ml autologous fat per patient (range 0.7-4 ml). An overcorrection was performed in all patients. RESULTS: All the patients showed improvements in whistle deformity. The mean resorption rate was 53% (range 30-80%). Three patients (20%) were not satisfied with the postoperative result. Six complications were assessed (4× feeling of pressure [27%], one hematoma [7%], one recurrent pain [7%]), but a major complication did not occur. REVIEW: We also present a review of the literature with different techniques that were described in the last 20 years. CONCLUSION: Autologous free fat graftings for reconstruction of whistle deformity represent a reliable method with a low complication rate. However, the resorption rate is unpredictable. If necessary, several autologous fat transplantations should be conducted at an interval of at least 6 months.

Recurrent mutations in NF-κB pathway components, KMT2D, and NOTCH1/2 in ocular adnexal MALT-type marginal zone lymphomas.

The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is still poorly understood. We analyzed 63 cases of such lymphomas for non-synonymous mutations in 24 candidate genes by amplicon sequencing. We validated frequent mutations in the NF-κB regulators MYD88, TNFAIP3 and TNIP1 in OAML, but also identified recurrent mutations in several additional components of the NF-κB pathway, including BCL10 and NFKBIA. Overall, 60% of cases had mutations in at least one component of NF-κB signaling, pointing to a central role of its genetic deregulation in OAML pathogenesis. Mutations in NOTCH1 and NOTCH2 were each found in 8% of cases, indicating a pathogenetic function of these factors in OAML. KMT2D was identified as the first epigenetic regulator with mutations in OAML, being mutated in 22% of cases. Mutations in MYD88 were associated with an inferior disease-free survival. Overall, we identified here highly recurrent genetic lesions in components of the NF-κB pathway, of NOTCH1 and NOTCH2 as well as KMT2D in OAML and thereby provide major novel insights into the pathogenesis of this B cell malignancy.

Use of dermis-fat grafts in the prevention of Frey's syndrome after parotidectomy.

OBJECTIVE: To examine the role of dermis-fat grafts in preventing gustatory sweating and in the reconstruction of facial contour defects after parotidectomy. PATIENTS: Twenty-three patients with tumours of the parotid gland were enrolled in this prospective clinical study from January 2006 to February 2014. All of them were evaluated for wound complications, Frey's syndrome, satisfaction, and tumour relapse. Follow-up periods ranged from 6 to 72 months. RESULTS: Nineteen patients completed the study. Nine complications observed in six patients were assessed (two haematomas [10%], one seroma [5%], one sialocele [5%], and recurrent pain in five patients [26%]). None revealed Frey's syndrome. Satisfactory results were found in relation to scar, facial contour, and overall outcomes. CONCLUSION: Dermis-fat grafts appear to be an effective method of preventing Frey's syndrome after parotidectomy. The stable long-term results and high patient satisfaction lead to the application of this operation technique in daily routine.

Nasal Entrance Correction in Unilateral Cleft Lip Repair.

PURPOSE: Correction of cleft nose deformity in patients with unilateral cleft lip is challenging and involves primarily the nasal cartilage and the nasal entrance. No consensus on the most effective surgical technique has been reached. This article describes a surgical procedure for nasal entrance correction. PATIENTS AND METHODS: In this retrospective study, 30 adult patients underwent secondary nasal entrance corrections. According to a modified Van der Meulen technique, a nasal alar rim flap with anatomic repositioning of the alar cartilage was applied. Symmetry and esthetic results were evaluated by semiquantitative photographic analysis. RESULTS: In all patients, the nasal tip was narrowed considerably, and a lifting of the nasal tip was achieved. Columellar elongation averaged 40%, and the form of the nostril was changed from horizontally oval to longitudinally oval. CONCLUSION: The described technique is well suited for a sustainable correction of complex cleft-induced deformities without visible scars in adult patients.