[Clinical and sonographic examination findings in patients with carotid-cavernous sinus fistulas]. / Klinische und echographische Untersuchungsbefunde bei Patienten mit Carotis-Sinus-cavernosus-Fisteln.

BACKGROUND: Symptoms and clinical findings in patients with carotid-cavernous fistulas are specific. Nevertheless, they can be very mildly expressed. This study aims to point out the potential diagnostic value of ultrasound of the orbit. METHODS: A total of 25 patients with a reliable angiographic diagnosis of a fistula were reviewed retrospectively. We analyzed the symptoms, clinical findings and demonstrability in ultrasound of the orbit. RESULTS: The most common clinical findings were nerve palsy, dilation of episcleral vessels and exophthalmos. If an ultrasound had been part of the examination a dilation of the superior ophthalmic vein could be demonstrated in all cases. CONCLUSION: The expeditious ultrasound investigation provides valuable information for the diagnosis of red eyes which are resistant to treatment. The examiner has to consider a fistula and perform an ultrasound especially when diplopia has newly occurred. Finally, the expedient neuroimaging can be arranged.

[Sympathetic ophthalmia following repeated pars plana vitrectomy : Clinical findings and spectral domain OCT follow-up]. / Sympathische Ophthalmie nach zweimaliger Pars-plana-Vitrektomie : Klinische Befunde und Spectralis-OCT-Verlauf.

Sympathetic ophthalmia is a rare form of bilateral granulomatous panuveitis, occurring after penetrating trauma. Hitherto, sympathetic ophthalmia after vitrectomy has only occasionally been described in the literature. This case report presents a female patient with sympathetic ophthalmia after repeated pars plana vitrectomy on the basis of clinical findings and follow-up with fluorescein angiography, spectral domain OCT, and histopathology.

[Therapy options for malignant eyelid tumors]. / Therapie bei malignen Lidtumoren.

Basal cell carcinomas are the most common malignant tumors of the eyelids. Patient history, clinical symptoms and signs, inspection, palpation and slit-lamp examination usually allow a working diagnosis; however, the clinical diagnosis requires histopathological confirmation and determination of the histopathological type. Squamous cell carcinomas, sebaceous gland carcinomas, melanomas and Merkel cell carcinomas can metastasize usually via the lymph vessels into the regional lymph nodes. Microscopically controlled excision of the primary tumor into healthy tissue is most commonly the first goal. Palpation and ultrasonography of the regional lymph nodes and also computed tomography (CT) with contrast enhancement and magnetic resonance imaging (MRI) for tumors with perineural sheath cell invasion are necessary to define the TNM stage. Non-surgical treatment options are becoming more popular in the further management of malignant eyelid tumors.

[Pathology and prognostic factors of conjunctival melanoma]. / Pathologie und Prognosefaktoren konjunktivaler Melanome.

BACKGROUND: Conjunctival melanoma is a rare but potentially fatal disease. The 10-year melanoma mortality can be up to 30 %, recurrence rates after treatment up to 50 % and the overall incidence of metastasis is 26 %. Improved treatment options are needed to increase the tumor-free survival of affected patients. OBJECTIVES: The aim of the study was to perform clinical and pathological staging using the TNM classification and to correlate the results with treatment modalities and recurrence rates. MATERIAL AND METHODS: The study included a case series of 80 eyes from 80 patients (42 females and 38 males, age 28-90 years) with histopathologically proven conjunctival melanoma studied by reviewing medical records, pathology reports and color photographs. The main evaluated characteristics were demographic information, tumor size, thickness, pathological diagnosis, BRAF mutation testing, clinical and pathological staging, recurrence, metastasis and duration of follow-up (mean 48 months). RESULTS: The lesions predominantly involved the bulbar conjunctiva (60 %) and other sites that were less often involved were the palpebral conjunctiva (23 %), conjunctival fornix (22 %) and lacrimal caruncle (15 %). Of the tumors 36 % were TNM classified as pTis, 34 % as pT1, 20 % as pT2 (palpebral, fornix and caruncle) and 10 % as pT3. Local recurrences were noted in 36 % of the patients (18 % Tis, 26 % T1, 32 % T2 and 70 % T3) and regional and distant metastasis in 20 % of the patients (0 % Tis, 10 % T1, 15 % T2 and 60 % T3). DISCUSSION: In this study increasing T stages were more often associated with recurrences and metastasis. Future studies correlating the TNM staging with histopathological and genetic predictors may help to improve the management of patients with conjunctival melanoma.

[Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma]. / Immuntherapie beim Aderhautmelanom: Vakzination gegen Krebs. Multizentrische adjuvante Phase-III-Impfstudie mit Tumor-RNA-beladenen dendritischen Zellen bei neu diagnostizierten, großen Uveamelanomen.

Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis.

[Trauma of periorbital soft tissue. Reconstruction with regard to functional and aesthetic aspects]. / Trauma der periorbitalen Weichteile. Rekonstruktion unter funktionellen und ästhetischen Gesichtspunkten.

Complex midfacial trauma requires interdisciplinary management. A wide range of reconstructive procedures are needed and if necessary secondary and even tertiary interventions should be performed at the appropriate time. We present the case of a 45-year-old man who was involved in a car accident and presented with severe injuries to the periorbital soft tissue. The focus was on the reconstruction of this sensitive region with regard to functional and aesthetic aspects. In view of the severity of the injuries the final clinical status is considered to be very important. Special issues and pitfalls in the reconstruction of trauma cases and potential management are discussed.

[A 2-year-old patient with acute proptosis]. / Zweijähriger Patient mit akutem Exophthalmus.

Hemorrhage into an orbital lymphangioma can cause acute proptosis. A lymphangioma must be distinguished from acute threatening causes of rapidly developing proptosis in childhood, such as orbital cellulitis or malignant tumors (rhabdomyosarcoma). Imaging (magnetic resonance imaging, ultrasound, computed tomography) and histopathological evaluation are required for the final diagnosis. Immunohistochemical staining of lymphatic vessels with podoplanin can be useful for confirmation of the diagnosis.

[Micronodular thickening of eyelid margins. Initial findings of a general disease]. / Mikronoduläre Verdickungen der Lidränder. Erstbefund einer Allgemeinerkrankung.

A 9-year-old boy presented with bilateral chronic thickening of the upper and lower eyelid margins with bead-like papules. The voice was hoarse due to a previously diagnosed thickening of the vocal cords. There was a history of recurrent abscesses of the parotid gland and of attention deficit hyperactivity disorder (ADHD).The eyelid changes were recognized as monoliform blepharitis and the diagnosis of lipoid proteinosis (Urbach-Wiethe disease) was confirmed by eyelid biopsy. The diagnosis of this systemic disease explained the other signs and symptoms of the patient.

[Selective lacrimal sac biopsy for external dacryocystorhinostomy: a clinical pathological study]. / Selektive Tränensackbiopsie bei externer Dakryozystorhinostomie: Eine klinisch-pathologische Studie.

BACKGROUND: Tumors of the lacrimal drainage system are rare but potentially life-threatening. The purpose of this study was to investigate the applicability of selective lacrimal sac biopsy in 500 cases of external dacryocystorhinostomy for acquired dacryostenosis. PATIENTS AND METHODS: Lacrimal sac biopsy was obtained selectively for atypical clinical and/or intraoperative findings. The frequency and spectrum of biopsies were recorded and correlated with the follow-up results. RESULTS: Lacrimal sac biopsy was performed in 19 external dacryocystorhinostomies (3.8%) including non-Hodgkin B-cell lymphoma (3), squamous carcinoma (2), mucoepidermoid carcinoma (1), malignant melanoma (1), oncocytoma (1), pyogenic granuloma (4), Wegener's granulomatosis (4) and sarcoidosis (3). Within 5 years none of the patients without biopsy developed systemic inflammatory diseases or lacrimal neoplasms. The 5-year survival was 87% in patients with significant lacrimal sac pathology and 96% in patients without significant pathology. CONCLUSION: External dacryocystorhinostomy with selective biopsy for atypical clinical and intraoperative findings allows safe diagnosis and management of potentially life-threatening lacrimal lesions.

[Nodular fasciitis of the eyelid and anterior orbit in children: case report and review of the literature]. / Noduläre Fasziitis im Kindesalter im Bereich des Lids und der vorderen Orbita: Kasuistik und Literaturübersicht.

An 8-year-old boy presented with a 6-week history of a rapidly progressive erythematous swelling of the right upper eyelid. Ultrasonography and magnetic resonance imaging revealed a subcutaneous nodular mass of the right upper eyelid medially with extension into the anterior orbit. The clinical differential diagnosis included rhabdomyosarcoma. A transcutaneous excisional biopsy was performed, and histopathologic examination confirmed the diagnosis of nodular fasciitis. Five years after surgery, there is no evidence of local recurrence, and the result is aesthetically satisfactory.

[Neuroradiological diagnosis and interventional therapy of carotid cavernous fistulas]. / Neuroradiologische Diagnostik und interventionelle Therapie bei Carotis-cavernosus-Fisteln.

Carotid cavernous fistulas are pathologic connections between the internal and/or external carotid artery and the cavernous sinus. According to Barrow one can distinguish between direct (high flow) and indirect (low flow) fistulas, whereby direct fistulas are often traumatic while indirect fistulas more frequently occur spontaneously in postmenopausal women. Diagnosis can easily be established using MRI and angiography, which allow exact visualization of the anatomy of fistulas to plan the interventional neurological therapy that in recent years has replaced surgical therapy. This article provides an overview on imaging findings, diagnosis using MRI and angiography as well as interventional treatment strategies.

Deletions of BRCA1/2 and p53 R248W gain-of-function mutation suggest impaired homologous recombination repair in fragile histidine triad-negative sebaceous gland carcinomas.

BACKGROUND: Sebaceous gland carcinomas represent rare malignancies of the skin and some 60% of them demonstrate high-grade microsatellite instability on the background of a defective mismatch repair system. However, a significant fraction of periocular sebaceous gland carcinomas exhibits microsatellite stability associated with a frequent loss of the candidate tumour suppressor fragile histidine triad (FHIT). OBJECTIVES: We hypothesized that in those sebaceous gland carcinomas with microsatellite stability and loss of FHIT, effector molecules participating in homologous recombination repair (HRR), such as BRCA1/2, could be somatically inactivated. METHODS: A pilot series of 10 paraffin-embedded sebaceous gland carcinoma specimens with a defined FHIT status was studied for loss of heterozygosity (LOH) events in the genes BRCA1, BRCA2, FHIT and WWOX. We sequenced the coding exons 5-8 of the p53 gene. RESULTS: Sebaceous gland carcinomas with FHIT negativity displayed LOH and biallelic deletions of the BRCA1 gene in five of 10 (50%) of the sebaceous gland carcinoma specimens analysed. Tumour-specific genomic losses close to BRCA2 were also uncovered. A homozygous p53 R248W gain-of-function mutation as the result of a CGG to TGG transition was identified in one of seven sebaceous gland carcinomas. It has been demonstrated previously that p53 R248W mutants inactivate ATM-directed HRR. This particular sebaceous gland carcinoma presented with concomitant genomic deletions at the BRCA1 and BRCA2 loci, and also at the constitutively fragile sites FRA3B/FHIT and FRA16D/WWOX. CONCLUSIONS: Our study demonstrates for the first time that microsatellite-stable FHIT-negative sebaceous gland carcinomas accumulate mutations that target central components of the HRR network. This observation will prompt investigations in synthetic lethality of BRCA-deficient sebaceous gland carcinomas by therapeutic poly(ADP-ribose) polymerase inhibitors.

[Malignant melanoma of the lacrimal sac]. / Malignes Melanom des Tränensacks.

A 68-year-old woman presented with a 10-month history of right-sided epiphora, bloody tears, and medial canthal mass. Computed tomography revealed a soft tissue mass of the right lacrimal sac with widening of the bony nasolacrimal canal. External dacryocystorhinostomy with incisional biopsy confirmed the diagnosis of malignant melanoma. After staging, further therapy included orbital exenteration, lateral rhinotomy with en bloc resection of the lacrimal drainage apparatus, and adjuvant radioimmunotherapy. One year after surgery, no evidence of local recurrence or metastatic disease could be detected.

Aggressive metastasising adenocarcinoma of the retinal pigment epithelium with trisomy 21.

This case report describes a 37-year-old man with a blind eye with opaque media. Histopathology revealed an aggressive adenocarcinoma of the retinal pigment epithelium with marked invasion of the choroid, retina, sclera and--not previously reported--the orbital and cranial optic nerve and subarachnoid space. The tumour seeded into the lumbar spinal-cord space. Metastatic foci--not in continuity with the primary process--developed in the parietal lobe and cerebellopontine angle. Adenocarcinoma of the retinal pigment epithelium, which occurs rarely in longstanding blind eyes, may exhibit aggressive behaviour with life-threatening risk of metastatic spread.

[Enophthalmos correction in complex orbital floor reconstruction : computer-assisted, intraoperative, non-contact, optical 3D support]. / Enophthalmuskorrektur bei komplexer Orbitarekonstruktion : Computerassistierte, intraoperative, berührungsfreie, optische 3D-Unterstützung.

In the case of displacement of the globe such as enophthalmos induced by trauma, the patient is affected on both counts: function and aesthetics. To prevent double vision or conspicuous asymmetry, exact correction of the globe position is required. The aim of this case report is to demonstrate an intraoperative computer-assisted, non-contact, optical 3D procedure for identification of the globe position to aid in placing the eyeball in the position required in complex reconstruction of the orbital floor. A 33-year-old man presented with a sunken eye on the right side in the horizontal and vertical plane 6 months after having undergone surgery elsewhere for a zygomatico-orbital fracture, also including the orbital floor. The patient was affected by double vision and a noticeable defective globe position. In planning the correction of the globe position, a three-dimensional image of the face with opened eyes was made with the optical sensor. Automatic comparison of symmetry revealed enophthalmos of 4 mm on relative en- and exophthalmometry. The decision was made to lift the orbital floor with a split calvarial bone graft. During surgery the position of the globe was also controlled by the three-dimensional optical technique. At the end of surgery there was exophthalmos of 1 mm. Six weeks after surgery the patient was not affected by any double vision. After 3 and 24 months enophthalmos was 1 mm. This case demonstrates how the non-ionizing, non-contact, optical 3D technique can help in planning, intraoperative transformation, and clinical monitoring to identify the correct position of the corneal vertex in complex orbital floor reconstruction.

[Differential diagnosis and treatment options for conjunctival tumors]. / Differenzialdiagnose und Therapieoptionen bei Tumoren der Konjunktiva.

The diagnostic classification of most conjunctival tumors is based on case history, inspection, and examination with the slit lamp microscope. Further imaging procedures are rarely indicated when malignant processes are not circumscribed. Clinical classification then also includes palpation and echographic examination of regional lymph nodes. Pigmented and nonpigmented melanocytic nevi are the most frequent conjunctival tumors. An important practical biomicroscopic cardinal symptom of the most frequent nevi is the presence of epithelial pseudocysts. Essential in practice is the histopathological confirmation of the clinical diagnosis, e.g., distinguishing between nonpigmented melanomas and sebaceous gland carcinomas with a pagetoid growth pattern or squamous cell carcinomas. Depending on the course and findings, the following therapeutic measures can be indicated: cryotherapy, chemotherapy, radiotherapy, modified enucleation, orbital exenteration, or a combination of different methods.

Epigenetic silencing contributes to frequent loss of the fragile histidine triad tumour suppressor in basal cell carcinomas.

BACKGROUND: Extensive exposure to ultraviolet radiation is associated with genetic alterations in basal cell carcinomas (BCCs), which represent some 75% of skin cancers. OBJECTIVES: As recent data suggested the fragile histidine triad (FHIT) gene product to participate in DNA damage responses we wished to address whether functional deletion of this tumour suppressor participates in the development of BCC. Our study focused on epigenetic inactivation of the FHIT gene. METHODS: Paraffin-embedded specimens from 17 patients with BCC were available for methylation-specific polymerase chain reaction (MSP), combined bisulphite-dependent restriction analysis (COBRA) of the FHIT gene and immunohistochemistry of its product. RESULTS: We report for the first time that 100% of BCCs are negative for FHIT by immunostaining. Aberrant methylation of the FHIT promoter occurred in a significant portion of BCCs. MSP detected hypermethylation of the FHIT/FRA3B locus in nine of nine (100%) periocular BCCs and in six of eight (75%) BCCs from other body regions. COBRA yielded similar results, confirming that some 88% of the 17 BCCs analysed harbour epigenetic silencing of the FHIT gene. Loss of FHIT protein was demonstrated immunohistochemically, confirming that promoter hypermethylation correlated with loss of gene expression. CONCLUSIONS: We have identified epigenetic silencing of the FHIT tumour suppressor gene as a frequent inactivation mechanism which is likely to contribute to functional deficiencies in DNA damage response of BCCs.

Different genetic pathways in the development of periocular sebaceous gland carcinomas in presumptive Muir-Torre syndrome patients.

Periocular sebaceous gland carcinomas (SGCs) occur in the eyelids either sporadically or as a phenotypic feature of Muir-Torre syndrome (MTS). In knockout mice mismatch-repair (MMR) defects or inactivation of the fragile histidine triad (FHIT) gene are associated with MTS-like signs, including SGC. To dissect the genetic alterations associated with microsatellite instability (MSI) and inactivation of the FHIT gene, we studied nine periocular SGC specimens from MTS patients. Immunohistochemistry was performed for FHIT, MSH2, MLH1, and MSH6. We assessed MSI as well as loss of heterozygosity (LOH) at the FHIT locus with polymorphic markers and genomic multiplex PCR. Epigenetic silencing was detected by methylation-specific PCR (MSP) and combined bisulfite restriction analysis (COBRA). Our analyses identified two SGCs with FHIT positivity and high-grade MSI, and seven cases with loss of FHIT and microsatellite stability (MSS). MSI correlated with loss of MSH2 and MLH1 immunostaining. Loss-of-function mechanisms affecting the FHIT gene were identified as intragenic deletions eliminating the coding exons 5 and 6 on one hand, and complete biallelic methylation of the FHIT transcription regulatory region on the other hand. Germinal FHIT mutations as a predisposing factor for MTS were excluded in two index patients with cancer in three generations, including an FHIT-negative SGC. Our data suggest that either somatic inactivation of the FHIT gene associated with MSS or inactivation of the MMR system resulting in MSI contribute to the development of periocular SGCs in presumptive MTS.

Management of spontaneous enophthalmos due to silent sinus syndrome: a case report.

Silent sinus syndrome (SSS) is a rare disease exhibiting unilateral enophthalmos and hypoglobus. A 26-year-old white female presented with right side enophthalmos and hypoglobus. There was no history of previous trauma or maxillary sinus diseases. A CT scan showed an opacified right maxillary antrum with decreased volume and downward bowing of the right orbital floor. From clinical and radiological findings the diagnosis SSS was made. Biopsies were collected from the maxillary sinus for the exclusion of malignancy. Two months later orbital floor reconstruction was carried out. Before antrostomy of the affected maxillary sinus, a relative enophthalmos of 4mm was determined. Five days after antrostomy the value reduced to 2.3mm. During the following 2 months the enophthalmos remained constant. At the end of the operation for orbital floor reconstruction it was 0.1mm. Five days after surgery the relative enophthalmos increased to 0.8mm. The value remained constant during the following 3 months. Initial antrostomy of the affected maxillary sinus may lead to a relevant, spontaneous reduction of enophthalmos. After a minimum period of 2 months a re-evaluation should be made, if a reconstruction of the orbital floor is still necessary for the correction of the globe position.