[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.

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.

Hertel exophthalmometry versus computed tomography and optical 3D imaging for the determination of the globe position in zygomatic fractures.

It has been the aim of the present study, to introduce the combination of computed tomography and optical 3D imaging to exophthalmometry and to compare the resulting data to the classic Hertel method. Twenty patients without orbital pathology and 12 patients were included in the study, who were subjected to a preoperative computed tomography. Optical 3D images of the facial surface were assessed and Hertel exophthalmometry was carried out to determine protrusion. In patients with zygomatic fractures the assessment of optical 3D images and Hertel values was repeated 5 days after surgery. Preoperative axial CT slices and postoperative optical contours through the globes were superimposed and the change in protrusion was determined. The protrusion values assessed either by CT, Hertel exophthalmometry or optical 3D imaging for patients without orbital pathology did not show any statistically significant differences between each other. For zygomatic fractures, Hertel exophthalmometry revealed more pronounced protrusion data in four of five cases of a posterolaterally dislocated lateral orbital rim and a higher degree of enophthalmos in cases without dislocation of the lateral orbital rim than it could be proved in the CT slices. The differences between optical measurements and CT data were minimal in patients with zygomatic fractures. The combination of computed tomography as baseline measurement and optical 3D imaging for the follow-up examinations reveal more realistic data in cases of zygomatic fractures than Hertel measurements and should be preferred.

Surgery for primary basal cell carcinoma including the eyelid margins with intraoperative frozen section control: comparative interventional study with a minimum clinical follow up of 5 years.

AIM: To assess recurrence of primary basal cell carcinoma (PBCC) including the eyelid margins after resection with or without intraoperative frozen section control (IFS). METHODS: Comparative non-randomised interventional study involving review of records of consecutive patients with histological diagnosis of PBCC including the eyelid margins, treated surgically at the University of Erlangen-Nürnberg between 1989 and 1998. Patients with a minimum clinical follow up of 5 years treated with (group I) or without (group II) IFS were compared. Postoperatively, permanent paraffin sections were available in all patients. RESULTS: 165 patients were available for study. There were 145 patients with a minimum of 5 years follow up. Of these, no tumour recurrences were observed in group I (n = 114) compared with three (9.7%) in group II (n = 31) (p = 0.002). CONCLUSIONS: Surgery for PBCC including the eyelid margins with IFS and immediate plastic reconstruction, as performed in the present study, is associated with better long term cure compared with surgery with clinical control.

[Management of conjunctival malignant melanoma associated with primary acquired melanosis (PAM) using 0.02% mitomycin C eyedrops]. / Therapie maligner Melanome der Konjunktiva bei primär erworbener Melanose (PEM) mit Mitomycin-C-0,02%-Augentropfen.

BACKGROUND: The therapy of malignant diseases of the conjunctiva with local chemotherapy is an extension of the therapeutic options in this field. We report on our experience in the therapy of malignant melanomas of the conjunctiva associated with primary acquired melanosis (PAM). METHODS AND PATIENTS: Between March 1998 and April 2001, 13 patients with malignant melanoma of the conjunctiva associated with PAM (6 female; 7 male; mean age 57+/-13 years) were treated with local chemotherapy. The tumor was classified as stage pT2 (pN0, pM0) in seven patients, stage pT3 (pN0, pM0) in three patients and in the remaining three patients the lid was involved in the malignant process (pT4, pN0, pM0). Local chemotherapy (mitomycin C 0.02% eyedrops 5 times a day) was applied after incisional biopsies in 2 cycles for 14 days with a 14-day break. In 4 patients a third cycle was included. RESULTS: Regression of the tumor was observed after completion of the therapy in all cases. Severe ocular or systemic secondary effects were not seen in our patients. Nine patients were without recurrence within the follow-up time. In three patients, a recurrence of the disease was observed. In these cases, the eyelid was involved in the process. CONCLUSION: Local chemotherapy with mitomycin C is a useful option in the treatment of malignant melanomas of the conjunctiva associated with PAM if the tumor stage is pT3 or less. From our point of view the combination with incisional biopsy is of great benefit. Prognosis of conjunctival malignant melanomas involving the lid margin (pT4) is poor.

Biomolecular markers of malignancy in human uveal melanoma: the role of the cadherin-catenin complex and gene expression profiling.

In recent years there has been a trend towards conservative management of uveal melanoma (UM), aimed at preserving the eye and vision. Despite improvements with this approach, recurrent tumour and metastatic disease still occur, and the management remains problematic. As a result of these limitations, there is interest in gaining a greater understanding of molecular changes associated with aggressive disease patterns in UM. This might result in new, more effective and less toxic therapies as well as provide prognostic information for defining subgroups of patients with a less favourable prognosis as potential candidates for adjuvant therapies. Accumulating evidence over the past decade suggests that disturbance in the cadherin-catenin adhesion complex is critical in the process leading to invasion and metastasis of many cancers. The recent advent of DNA micro-array technology now offers an unprecedented ability to study these molecules and others associated with malignant transformation. In this mini-review, the aspects of tumour progression in which cadherin-catenin may be involved are dealt with along with the potential application of DNA micro-array technology to the problem in UM.

[Orbito-palpebral emphysema due to ethmoidal fracture]. / Orbito-palpebrales Emphysem bei Siebbeinfraktur nach Kopfprellung.

BACKGROUND: Orbito-palpebral emphysema is a frequent pathological entity due to head injury. We report on a patient and correlate the clinical view and computer tomography findings. CASE REPORT: A 17-year-old male was referred to our hospital after a blunt trauma to his head. Visual acuity was 1,0. Diplopia, restricted motility and exophthalmus about 4 mm were found. CONCLUSION: If swelling of the lid is found orbito-palpebral emphysema should be thought of to initiate appropriate therapy to avoid possible severe complications, for example, occlusion of the retinal central artery.

Orbital involvement in cherubism.

PURPOSE: To demonstrate the clinical, radiologic, and histopathologic features of a patient with orbital involvement in cherubism that prompted surgical treatment. DESIGN: Single interventional case report. INTERVENTION: Findings of the ophthalmic evaluation, computed tomography (CT) scans, intraoperative examination, and light microscopy of the specimens were analyzed. MAIN OUTCOME MEASURES: Globe displacement, orbital bony lesions detected on CT scans, histopathology, and postoperative results were assessed. RESULTS: A 27-year-old female was seen with a slowly progressive superonasal globe displacement and a temporal orbital mass bilaterally of 6 years' duration. She had a history of cherubism, but her cheeks and jaws had a normal appearance instead of the bilateral fullness of the lower half of the face typical of the disease. CT scans demonstrated multicystic bony lesions arising from the orbital floors bilaterally. The masses were excised using an anterior transcutaneous transseptal orbitotomy. Histopathology demonstrated numerous giant cells in a fibrovascular stroma, confirming the clinical diagnosis of cherubism. Postoperative recovery was complete. CONCLUSIONS: Orbital involvement in cherubism may develop beyond puberty, after stabilization or regression of the lesions in the jaws. Patients with cherubism should be routinely evaluated by an ophthalmologist.