Cutaneous SCC with orbital invasion: case series.

Cutaneous squamous cell carcinoma (cSCC) is the most common tumour entity that grows secondarily into the orbital area, while basal cell carcinoma (BCC) is the most common periocular and eyelid tumour. Diagnostic delays are common and may increase post-treatment complications. The therapy is challenging and must be discussed at an interdisciplinary tumour board. We discuss four cases of cSCC with orbital invasion treated with immune-checkpoint inhibitors with variable responses.

Acute Lid Swelling: a Series of Unusual Cases, Treatment and Follow-up.

BACKGROUND: There are many different aetiologies for acute lid swelling, including infection, inflammation, degeneration, tumours and trauma. We present five uncommon cases of acute lid swelling and give an overview of differential diagnoses for rapidly evolving eyelid swelling. HISTORY AND SIGNS: We reviewed the charts of five patients with initial presentation of acute lid swelling. For the five patients, there were diagnoses of Churg Strauss syndrome, an allergic reaction to hyaluronic acid, lymphangioma, a ruptured dermoid cyst and a co-infected pre-existing orbital lesion that was only evident in the follow-up. THERAPY AND OUTCOME: Individual patients required totally different treatments. A ruptured dermoid is a dramatic problem that demands immediate surgical attention. Swelling in sinusitis in a child is just as important, but requires antibiotic treatment, careful follow-up and subsequent treatment of any secondarily infected pre-existing lesion. The less dramatic first presentations were more difficult to diagnose and required protracted observation and immunosuppressive treatment. CONCLUSIONS: The key to success often lies in the assessment of the patient's history and correctly timed surgery. Dramatic first manifestations were often easier to treat than initially low grade lid swelling. Unclear results, such as a low grade eosinophilia, should not be ignored.

Intraocular Inflammation Associated with New Therapies for Cutaneous Melanoma - Case Series and Review.

Background. In advanced cutaneous melanoma, new systemic therapies include immunotherapy by checkpoint inhibition and targeted inhibition of the mitogen-activated protein kinase pathway; these are becoming increasingly well established. We describe the clinical presentation of uveitis in three patients with concomitant systemic melanoma treatment. History and Signs. Three patients with metastatic melanoma receiving systemic therapy (ipilimumab, vemurafenib) presented at our institution with a short history of ocular symptoms. Clinical findings included anterior uveitis, intermediate uveitis, disc swelling, inflammatory choroidal lesions and retinal vasculitis. Therapy and Outcome. All three patients responded well to local and/or systemic steroid treatment. In one case, the systemic anti-cancer drug was discontinued after the onset of uveitis. Conclusions. Ocular inflammation may occur in the setting of systemic melanoma therapy. Presentations of uveitis include Vogt-Koyanagi-Harada-like syndromes. Ocular inflammation can usually be controlled by topical and sometimes systemic corticosteroid therapy. However, treatment guidelines are not established and management of these patients demands close cooperation with the oncologist.

Lymphoma of the ocular adnexa.

BACKGROUND: Over the last decades, the incidence of ocular adnexal lymphomas has been increasing. Over the last decade advances in the imaging of ocular adnexal lymphomas have enabled precise biopsies of the tumors. Biopsies are necessary for immunophenotyping, correct molecular classification and the immediate start of the appropriate treatment. PATIENTS AND METHODS: In a retrospective study, we collected data from 16 patients (19 eyes) treated for lymphoma of the ocular adnexa between 2006 and 2011 with various tumor sites. We evaluated ocular symptoms of the patients in correlation to the tumor localization on imaging and determined the access of biopsy. Follow-up period (13.7 ± 15.4 months) and therapy were analyzed. RESULTS: The mean age of study patients was 67.4 ± 13.6 years. Seven patients presented with exophthalmos, 6 with upper lid swelling, 5 with double vision, 5 with reduced visual acuity and one patient with retinal detachment. None of the patients complained of pain. In 7 cases the location of the OAL was superior, in 6 retrobulbar, in 4 patients in the lacrimal gland (1 bilaterally affected), one case with lacrimal sac infiltration and another with isolated subconjunctival lymphoma. Patients with retrobulbar tumors complained of visual loss, whereas patients with anterior orbital tumors showed localized nodular swelling. In 11 cases (58%) the diagnosis was marginal zone B-cell lymphoma (MALT), in 5 (26%) follicular lymphoma. 11 patients (69%) received curative and one HIV-positive patient palliative radiation. Three patients were treated with systemic rituximab due to generalized lymphoma and one of them was complemented with CHOP therapy. One patient received chemotherapy alone (CHOP). During the follow-up the HIV-positive patient died. CONCLUSIONS: All our lymphoma patients showed full tumor regression, without side effects from radiotherapy. In this study we emphasize the need to perform a diagnostic biopsy. The risk of biopsy by a trained surgeon is small. Early and accurate diagnosis is crucial for proper treatment. In unclear situations repeated biopsies might be necessary.

Bisphosphonate-associated orbital inflammatory disease and uveitis anterior--a case report and review.

BACKGROUND: Drug-induced cases of orbital inflammation and uveitis are rare.We present a bisphosphonate-induced case of unilateral orbital inflammation and bilateral anterior uveitis. PATIENTS AND METHODS: A 75-year-old female presents because of pain and swelling around her left eye with an onset 2 days after an intravenous zoledronic acid therapy for osteoporosis. Examination reveals reduced visual acuity of 0.2, proptosis of 4 mm, marked conjunctival chemosis and hyperemia, ophthalmoplegia and choroidal folds in the left eye and a bilateral anterior uveitis. CT and MRI scans show signs of diffuse pre- and postseptal inflammation in the left orbit. RESULTS: Initiation of intravenous methylprednisolon leads to a complete regression of the inflammatory process within days. This causality between the therapy with bisphosphonates and an orbital inflammation as well as an anterior uveitis corresponds to the literature. Drug-induced cases of orbital inflammation and uveitis have also been reported following use of antiinfectious drugs, biologica and vaccines. CONCLUSIONS: Iatrogenic causes should be considered in the differential diagnosis of orbital inflammations, scleritis and uveitis. Findings are mostly reversible after discontinuation of the drug and therapy of inflammation.

[IgG4-related orbital inflammation]. / IgG4-assoziierte orbitale Entzündungen.

INTRODUCTION: Serum immunoglobulin G4 (IgG4)-related systemic disease is a newly found entity and should be considered as a further differential diagnosis to the big pool of unspecific orbital inflammation. We describe clinical appearance and treatment options. PATIENTS AND METHODS: We retrospectively analyzed all patients with the diagnosis IgG4-related orbital inflammation who were examined in our outpatient clinic. We compared symptoms, clinical and histological findings and therapy. RESULTS: In the last 17 months five patients were diagnosed with IgG4-related orbital disease. Biopsies were performed of most affected areas as seen in the computerised tomography scan. Histology revealed marked infiltration with IgG4-positive plasma cells. Serum IgG4-levels were partly significantly elevated. Based on these findings diagnosis of an IgG4-related disease was agreed and treatment with oral prednisone installed. In one patient a therapy with Rituximab was successfully started. CONCLUSION: Extended unspecific orbital inflammation, especially when bilateral and associated with systemic disease should be considered to be IgG4-related. Histological proof of IgG4-positive plasma cells and elevated IgG4 serum levels do confirm this diagnosis. Strict follow-up and interdisciplinary work-up is recommended.

[Early surgical rehabilitation due to modified exenteration technique]. / Frühe chirurgische Rehabilitation durch modifizierte orbitale Exenteration.

BACKGROUND: Orbital exenteration is a life intruding surgical procedure with severe functional, aesthetic and psychological consequences. Apart from the correct tumor treatment, early aesthetic and psychosocial rehabilitation is crucial for the well-being of the patient. We discuss reasons leading to exenteration and present new surgical techniques. Local flaps in the anterior socket improve wound healing allowing early placement of the prosthesis and therefore faster social rehabilitation of the patient. PATIENTS AND METHODS: Between 2007 and 2011 seven patients with malignant orbital tumors (1 × plasmocytoma, 1 × melanoma, 1 × sarcoma, 1 × squamous cell carcinoma and 3 × basal cell carcinoma) received a radical orbital exenteration at the Department of Ophthalmology of the Zurich University Hospital. The medical histories were evaluated according to reasons for exenteration, surgical techniques and postoperative follow-up. Reconstruction of the anterior socket border succeeded using local flaps (Mustardé, Glabella and combined with further modified pedicled local full thickness skin flaps). The central defects were covered with split skin graft from the thigh. RESULTS: Three weeks after surgery the anterior border of the socket was completely healed without problems by local flaps with good blood supply. This allowed the early prosthetic fitting and wearing as well as quick social rehabilitation of the patient. CONCLUSIONS: The use of local flaps improves wound healing even in anticoagulated patients. This reduces the time of hospitalization and rehabilitation, and allows an early, satisfactory, social reintegration of the patient.

[Hypoglobus--illusive or real? Etiologies of vertical globe displacement in a tertiary referral centre]. / Hypoglobus--Schein oder Sein? Ätiologien vertikaler Bulbusdislokationen in einem tertiären Zentrumsspital.

BACKGROUND: While exophthalmus is quantifiable with readily available measurement tools, there is no such tool for hypoglobus/hyperglobus. Despite its possible life-threatening causes only few articles address the etiologies of vertical globe displacement in the current literature. The aim of our study was to describe etiologies of hypoglobus and to analyze the ratio of malignant diseases. PATIENTS AND METHODS: 3000 portrait photographs taken in our ophthalmology department between 2005 and 2009 were retrospectively screened for patients with vertical globe displacement. Pictures were assessed by three independent ophthalmology-trained observers and matched to the diagnosis based on patient records. RESULTS: 95 patients with supposed vertical globe displacement were identified. Vertical globe displacement was due to an intracranial or orbital disease in 45 patients including 6 patients with a malignant disease. Additional 10 patients had thyroid associated orbitopathy. 11 patients turned out to have mere facial asymmetry, 26 patients had strabism and four patients had an ocular prosthesis. CONCLUSIONS: The etiologies of hypoglobus ranges from orbital fractures to life-threatening malignant tumors. Distinction between apparent and true hypoglobus can be challenging.

[Solitary fibrous tumour of the orbit: clinical, radiological, histological findings and differential diagnosis of an uncommon tumour]. / Solitärer fibröser Tumor der Orbita: klinische, radiologische, histologische Merkmale und Differenzialdiagnose eines ungewöhnlichen Tumors.

BACKGROUND: Solitary fibrous tumours (SFT) are mesenchymal neoplasias rarely found in the orbit. Due to their sharp delineation they are frequently mistaken for various benign neoplasma, such as cavernous hemangiomas, neurinomas and pleomorphic adenomas. We present two cases of SFT in the orbit and one in the lacrimal sac and discuss the radiological and histological differential diagnosis. PATIENTS AND METHODS: Among 9 patients diagnosed and operated in our department between 2008 and 2010 with an orbital tumour, three had the histological diagnosis of a solitary fibrous tumour. In 5 cases an MRI scan was performed preoperatively, in 4 cases a CT scan. RESULTS: Histology showed 2 pleomorphic adenomas, 2 cavernous hemangiomas, 2 neurinomas and 3 SFT. All SFT were intraoperatively well circumscribed and enucleated, showing histologically incomplete resection. No further treatment was given. There is no recurrence in any of the patients in the follow up of an average of 10 months (range 1 - 30 months). CONCLUSIONS: SFT are rare mesenchymal tumours of the orbit. The radiological differential diagnosis is difficult and they can be mistaken for more common tumours. The SFT has a wide range of histological appearances. Long term clinical follow-up is mandatory in all cases of SFT.

[Eyeball perforation of a 7-year-old girl caused by the "Must-Have Office Toy 2017" : The potential risk of injury by a spinning toy (fidget spinner)]. / Bulbusperforation eines 7­jährigen Kindes durch das "Must-Have Office Toy 2017" : Das potenzielle Verletzungsrisiko eines Handkreisels ("fidget spinner").

A 7-year-old girl presented to the emergency department of the eye clinic with an eyeball perforation with iris prolapse and corneal as well as scleral wounds of the left eye caused by a spinning toy (fidget spinner). A surgical wound inspection with iris reposition and corneal and scleral suture were performed without delay. This case report demonstrates the potential risk of this popular toy.

Induction of Cyp1a-1 and Cyp1a-2 gene expression by a reconstituted mixture of polynuclear aromatic hydrocarbons in B6C3F1 mice.

The potential non-additive interactions of polynuclear aromatic hydrocarbon (PAH) mixtures as inducers of Cyp1a-1 and Cyp1a-2 gene expression were investigated in B6C3F1 mice using a reconstituted PAH mixture. The chemical composition (% by weight) of the reconstituted PAH mixture was: 2-ring PAHs--indan (0.22), naphthalene (23.8), 2-methylnaphthalene (23.2) and 1-methylnaphthalene (13.3); 3-ring PAHs--acenaphthylene (7.7), acenaphthene (0.6), dibenzofuran (0.7), fluorene (4.3), phenanthrene (10.5) and anthracene (3.4); > or = 4-ring PAHs--fluoranthene (2.4), pyrene (4.3), benz[a]anthracene (1.4), chrysene (1.5), benzo[b]fluoranthene (0.8), benzo[k]fluoranthene (0.9) and benzo[a]pyrene (0.9). The composition of the 2-, 3- and > or = 4-ring PAH fractions were based on the relative concentration of individual PAHs as noted above. The > or = 4-ring PAH fractions were based on the relative concentration of individual PAHs as noted above. The > or = 4-ring PAH fraction and reconstituted mixture induced hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity and Cyp1a-1 mRNA levels, whereas the 2- and 3-ring PAHs were only weakly active. Direct comparison of the potencies of the reconstituted mixture and > or = 4-ring PAHs showed that the Cyp1a-1 induction activity of the reconstituted mixture was due to the > or = 4-ring PAHs. The reconstituted PAH mixture and > or = 4-ring PAHs also induced Cyp1a-2 hepatic mRNA levels and microsomal methoxyresorufin O-deethylase (MROD) activity; however, their dose-response curves indicated that the reconstituted PAH mixture was more potent as a Cyp1a-2 inducer than the > or = 4 ring PAHs. The differences in potency were due to 3-ring PAHs which were found to be strong inducers of hepatic Cyp1a-2 mRNA levels and microsomal MROD activity at the lowest dose administered (37 mg/kg). The 3-ring mixture caused a maximal 29-fold increase in hepatic MROD activity at a dose of 292 mg/kg, but only 28% of maximal induction of EROD activity. Northern analysis of liver mRNA from mice treated with 3-ring PAHs showed that there was minimal induction of Cyp1a-1 mRNA levels. The 3-ring PAHs did not competitively bind to the mouse hepatic cytosolic aryl hydrocarbon (Ah) receptor suggesting that 3-ring PAHs are a new class of Cyp1a-2 inducers which do not act through the Ah receptor.

Synergistic activity of polynuclear aromatic hydrocarbon mixtures as aryl hydrocarbon (Ah) receptor agonists.

The relative potencies of benzo[a]pyrene and a complex mixture of polynuclear aromatic hydrocarbons (PAHs) produced as by-products of manufactured gas plant (MGP) residues as inducers of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity were determined in the B6C3F1 mouse. The ED50 values for the induction response were 78 and 65 mg/kg for benzo[a]pyrene and the MGP-PAH mixture, respectively. Analysis of the MGP-PAH mixture indicated that benzo[a]pyrene and other compounds containing four or more rings and which are known to induce EROD activity were only present as trace components of this mixture. A comparison of the EROD induction potencies of benzo[a]pyrene and the MGP-PAH mixture showed that the mixture was approximately 706 times more potent than expected based on its benzo[a]pyrene content (0.17%). This induced P-450 activity could significantly increase the metabolism of the carcinogenic PAHs and thereby modulate the overall carcinogenicity of the mixture. The apparent synergistic activity of the MGP-PAH mixture was further investigated by comparing the activities of this mixture and benzo[a]pyrene for several other aryl hydrocarbon (Ah) receptor-mediated responses including (i) induction of hepatic CYP1A1 mRNA levels, (ii) transformation of the rat cytosolic Ah receptor to a complex which binds to a dioxin responsive element, (iii) induction of EROD activity and (iv) antiestrogenicity in MCF-7 human breast cancer cells, and (v) inhibition of the splenic plaque-forming cell (PFC) response to both T cell-dependent and independent antigens in B6C3F1 mice. For the EROD and CYP1A1 mRNA induction and cytosolic transformation activities and immunosuppressive effects, the MGP-PAH mixture was approximately 100-900 times more potent as an Ah receptor agonist than expected based on its benzo[a]pyrene content. The synergistic activity was lower (19-fold) for the antiestrogenic response in MCF-7 cells. The reason for the synergistic effects of the MGP-PAH mixture were not due to contamination of the mixture by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds and the results suggest that the enhanced potency of the mixture is due to unknown interactions between the individual PAHs present in the mixture.

The effect of pretreatment with ischaemic preconditioning or cromakalim on perfusion in skeletal muscle during ischaemia-reperfusion injury.

BACKGROUND: Ischaemia-induced damage of skeletal muscle may lead to side effects in orthopaedic and reconstructive surgery where tourniquet ischaemia is applied to ensure a bloodless operative field. In this study we investigated the effect of ischaemia-reperfusion injury with and without preconditioning by studying the skeletal muscle microcirculation. A further aim was to establish whether ischaemic preconditioning or pretreatment with cromakalim, a potassium channel opener reduces ischaemia-reperfusion injury. METHODS: Twenty-eight Wistar rats were randomised into four groups (n=7 per group). Group 1, control with no treatment; Group 2, two and a half hours tourniquet ischaemia followed by two hours of reperfusion to the left hindlimb. Furthermore, we pre-treated two groups prior to the ischaemia-reperfusion period; Group 3 with three short cycles of ischaemia-reperfusion (5'/5') and Group 4 pre treated with cromakalim (100 microg/kg bw). We monitored the gastrocnemius muscle blood flow in vivo. RESULTS: There were no significant changes in the skeletal muscle microcirculation and temperature at the baseline in the four groups (p=0.110). In the ischaemic reperfusion, ischaemia preconditioning and cromakalim groups, the recorded skeletal muscle microcirculation during ischaemia decreased significantly (p<0.001) with respect to the baseline. In Group 2 the microcirculation recovered rapidly after release of the tourniquet, but was significantly lower (37 percent of baseline value, p<0.001) within two hours of reperfusion. In the ischaemia preconditioning group the microcirculation as in the ischaemia-reperfusion group recovered rapidly after release of the tourniquet, although failing to reach the baseline value within two hours of reperfusion. The mean microcirculation value of the left limb was slightly higher than Group 2 but significantly lower compared to the baseline after two hours of reperfusion (p<0.001). The change in the skeletal muscle microcirculation with cromakalim after two hours of reperfusion was not significant when compared to baseline values (p>0.05). The cromakalim group after two hours reperfusion had significantly higher microcirculation values when compared with Groups 2 and 3 (p<0.001). During ischaemia-reperfusion in Groups 2-4, there was no significant alteration in the systemic haemodynamic circulation. CONCLUSIONS: This study supports the hypothesis that cromakalim reduces postischaemic skeletal muscle damage and reperfusion injury.

Hypoglobus due to tumours in the superior orbital region.

BACKGROUND: Tumours in the superior orbital region can cause hypoglobus. We compare the pre- and postoperative globe position in two patients with different tumour types. HISTORY AND SIGNS: A 29-year-old man and a 58-year-old woman presented with pronounced hypoglobus. In both patients time-scale and importance of the lesion were comparable. Imaging suggested a pleomorphic adenoma in the younger patient, whereas the female patient was radiologically diagnosed with a hemangioma. THERAPY AND OUTCOME: Both radiological diagnoses could be histologically proven. Both lesions were excised in toto. The adenoma patient showed a full recovery of the preoperatively reduced vision. However, the hypoglobus persisted even after ten months. The hemangioma patient had an immediate full recovery of her hypoglobus. CONCLUSION: The histological type of a tumor in the superior orbit is of importance regarding the degree of reversibility of the accompanying hypoglobus.

[Intraorbital haematoma while scuba diving--a case report]. / Orbitale Blutung während eines Tauchganges--eine Fallvorstellung.

BACKGROUND: Intraorbital haematoma while scuba diving is a rare finding after barotrauma. MATERIAL AND METHODS: Case report. RESULTS: A 36-year-old woman presented with a swelling of the left lid after having dived to 10 m below sea level. The CT scan and MR imaging of the head revealed a retrobulbar intraconal haemorrhage within the left orbit. Three months after the accident the patient did not have any complaints, angiography could not detect any intracerebral vascular anomalies. As a complicating risk factor the patient had fibrous constrictions of both Eustachian tubes rendering the compulsory nasopharyngeal decompression process during scuba diving impossible. CONCLUSION: Vascular intracerebral anomalies which could be the potential cause for the described retrobulbar haemorrhage must be excluded so as to reduce the risk of recurrence.

Rapid progressive extramedullary plasmacytoma in the orbit.

BACKGROUND: Plasma cell tumors of the orbit are uncommon and mostly the first manifestation of a multiple myeloma (MM). Primary extramedullary plasmacytoma (EMP) of the orbit is exceedingly rare and only a few cases have been reported so far. Differentiation of an EMP from a MM is important, since 9.5 years have been reported as the mean survival of EMP, compared with a mean survival of 3 to 4 years for multiple myeloma. HISTORY AND SIGNS: A 68-year-old man presented with a history of rapid progressive extramedullary plasmacytoma in the right orbit, increasing in size within a few weeks. MR imaging revealed an intraorbital mass measuring 5.2 x 4.7 x 3 cm. The earlier performed biopsy was positive for plasmacytoma of the lambda light chain type. Systemic work-up was negative for further tumor spread. THERAPY AND OUTCOME: Irradiation (a maximum of 80 Gy) and several chemotherapy cycles showed no effect. Exenteration with sparing of the upper and lower lid skin was performed. The residual defect was covered by a Thiersch graft. Although the orbit had been irradiated with the maximal dose, the Thiersch graft healed well. CONCLUSION: Normally, EMP is slow to increase in size. In our patient, marked growth of tumor was noted within one week. One underlying reason is the poorly differentiated, blastic morphology leading to this rapid tumor growth. However, particular molecular features, like a t(4;14), could not be demonstrated.

[Eyelid chondroid syringoma: a case report]. / Syringome chondroïde de la paupière: à propos d'un cas.

Chondroid syringoma is a rare benign skin tumor of the head and neck. Only 15 cases presenting on the eyelid have been described in the literature. An 84-year-old patient presented with an 8-mm nodule on the right inferior eyelid that had grown over 5 years. The lesion was surgically removed, and the histopathological examination showed a chondroid syringoma. Knowledge of this disease is important because malignant transformations do occur.