Clinico-radiological findings of neuroendocrine tumour metastases to the orbit.

PURPOSE: We present the clinico-radiological findings of neuroendocrine tumour metastases to the orbit. METHODS: This was a multicentre, retrospective study of patients with neuroendocrine tumour metastases to the orbit. Data was collected from medical records across five different sites within Australia and the United Kingdom. RESULTS: Nine patients (eleven lesions) were identified. The most common presenting complaint was diplopia (5/9, 56%). Disease occurred bilaterally in two patients. Seven patients (78%) had extraocular muscle involvement. The lateral recti (4/9, 44%) and superior recti (2/9, 22%) were the most commonly affected. Ocular presentation preceded primary tumour diagnosis in three patients (33%). On orbital imaging, metastases were most commonly reported as well circumscribed, ovoid or round, heterogeneous, contrast-enhancing masses. Features of intralesional haemorrhage and bony invasion are uncommonly reported. CONCLUSIONS: Neuroendocrine tumour metastasis to the orbit is uncommon. Metastases have a propensity for the extraocular muscles, commonly presenting as heterogeneous, well circumscribed, contrast-enhancing lesions on neuroimaging. New ocular symptoms, a history of neuroendocrine tumours, and these radiological findings, should lead to high clinical suspicion of metastatic disease. Atypical findings warrant biopsy to exclude other causes of orbital lesions.

The 2017 Doyne Lecture: the orbit as a window to systemic disease.

A very large number of disorders affect the orbit, and many of these occur in the setting of systemic disease. This lecture covers selected aspects of orbital diseases with systemic associations in which the author has a particular clinical or research interest. Spontaneous orbital haemorrhage often occurs in the presence of bleeding diatheses. Thrombosis of orbital veins and ischaemic necrosis of orbital and ocular adnexal tissues occur with thrombophilic disorders, vasculitis, and certain bacterial and fungal infections. Non-infectious orbital inflammation commonly occurs with specific inflammatory diseases, including Graves' disease, IgG4-related disease, sarcoidosis, Sjögren's syndrome and granulomatosis with polyangiitis, all of which have systemic manifestations. IgG4-related ophthalmic disease is commoner than all these except Graves' orbitopathy. Some of these orbital inflammatory diseases are associated with an increased risk of B-cell lymphoma, usually marginal zone lymphoma of MALT type. Ocular adnexal lymphoma also has an association with infectious agents including Helicobacter pylori and Chlamydia psittaci. Orbital metastasis may be the first presentation of systemic malignancy. A number of orbital neoplasms occur in the setting of familial cancer syndromes, including Neurofibromatosis types 1 and 2. Study of the genetics and molecular biology of orbital diseases such as Graves' orbitopathy and idiopathic orbital inflammatory disease will yield useful information on their diagnosis and management.

Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review.

BACKGROUND/AIMS: Adult xanthogranulomatous disease involving the ocular tissues is rare and poorly understood. Adult onset xanthogranuloma (AOX), adult onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD) are the four syndromes within this disorder, which is diagnosed by characteristic histopathology. Experience with eight cases prompted a multi-institutional effort to study the histopathology, immunohistochemistry, clinical findings, and systemic associations in this disorder. METHODS: 22 cases, including histopathological slides, were compiled. Published reports were identified by an English language Medline search (1966-2005) and review of reference citations. Each case in this series and the literature was classified as one of four syndromes and then analysed for age onset, sex, skin xanthoma, orbital location, immune dysfunction, internal organ and bone lesions, treatment, and outcome. The histopathology in each of these cases was reviewed by two pathologists. Immunhistochemical stains (CD3, CD4, CD8, L26) were performed in 14 cases where unstained slides were available. RESULTS: 137 cases were compiled. There was no sex or age difference between syndromes. AOX, AAPOX, NBX affect the anterior orbit, ECD tends to be diffuse and intraconal. Skin lesions are found in all the syndromes. Immune dysfunction was noted in all cases of AAPOX and NBX; 11% of NBX and all ECD patients had internal organ disease. Treatment included surgery, corticosteroids, other chemotherapeutic agents, radiotherapy, and combinations of these. No AOX or AAPOX deaths occurred; 66% of ECD patients died. All 22 cases had xanthoma cells; most had Touton giant cells. Lymphocytes were present in all cases and occurred as aggregates (mostly in AAPOX) or diffuse populations mixed with fibroblasts (mostly in ECD). Immunohistochemistry revealed the majority of these to be CD8+. Necrosis was most marked in NBX. CONCLUSION: Adult xanthogranuloma of the orbit is rare, making prospective evaluation or meta-analysis impossible. The best treatment is unknown but seems to be with multiagent chemotherapy guided by histopathological, immunohistochemical, and systemic findings.

Growth and differentiation of human and murine erythroleukemia cell lines in serum-free synthetic medium.

Only two chemicals (transferrin and selenium dioxide) are required to supplement serum-free Roswell Park Memorial Institute Medium 1640 for long-term growth and for spontaneous and induced differentiation of established lines of human and mouse erythroleukemia cells. We describe here two serum-free media (a minimal synthetic medium and a high-density synthetic medium) that support the growth and differentiation of human K562(S) and mouse clones 745, 707, and 3TCl 12 erythroleukemia cell lines in long-term culture. The doubling times of the erythroleukemic cell populations are longer in minimal synthetic medium that in serum-containing medium. Cell saturation density in minimal growth medium is one-half that obtained in serum-containing medium for clone 745, whereas for K562(S) it is approximately the same. Cell saturation density in high-density medium (containing albumin) is greater than that achieved in serum-containing medium for K562(S), whereas for clone 745 cell saturation density increases for cells in midlogarithmic growth, although not to the density of cells grown in serum-containing medium. The differences in saturation density are due to a decreased doubling time as well as to better survival of the cells 3 or 4 days after plating. The cells can grow in the synthetic media and be passaged for as many generations as desired without impairment of growth capabilities. In the minimal synthetic medium, spontaneous differentiation of erythroleukemia cells continues to occur, indicating that spontaneously differentiating cells are the result of intracellular mechanisms controlling the expression of a genetic program of some of the cells at any given time. Hemoglobin synthesis can be induced in cells growing in synthetic medium by using lower concentrations of the same inducers that are effective in serum-containing medium, indicating that these chemicals do not depend on serum factors to initiate the process of differentiation. The percentage of benzidine-positive cells and the concentration of hemoglobin per cell, however, are less in the synthetic medium than in serum-containing medium, suggesting that serum factors do play a role in modulating the extent of hemoglobin synthesis. The types of hemoglobins synthesized by cells in synthetic medium are identical to those reported in serum-containing medium.

Differential expression of the globin genes in human leukemia K562(S) cells induced to differentiate by hemin or butyric acid.

Human leukemia K562(S) cells were induced to differentiate by 50 microM hemin or 1.4 mM butyric acid, and the types of hemoglobins synthesized were compared. In both cases, embryonal hemoglobins [Portland, Gower 1, Hb X, and fetal hemoglobin (Hb-F)] were detected. Butyric acid-treated K562(S) cells contained mostly Hb Gower 1 (zeta 2 epsilon 2) and a hemoglobin with the electrophoretic characteristics of Portland (gamma 2 zeta 2). For hemin-treated K562(S), the most abundant hemoglobin synthesized by Hb X (epsilon 2 gamma 2), and the second most abundant was Bart's (gamma 4). Traces of Gower 1 were observed in nontreated K562(S) cells. The kinetics of hemoglobin induction as a result of the two treatments differed; increased hemoglobin synthesis was detected after only 24 hr of hemin treatment, whereas 4 days were required in butyric acid-treated cells. Both hemin and butyric acid were able to induce their respective patterns of hemoglobin synthesis independent of the presence of serum in the K562(S) growth medium. Analysis of the globin chains in induced K562(S) cells induced to differentiate indicated that, with both inducers, adult alpha- but not beta-globin chains were present. Karyotype analysis of K562(S) cells revealed a nearly triploid chromosome complement with a modal number of 68 chromosomes. Three copies of chromosome 11 and four copies of chromosome 16 (coding for the beta-like and alpha-like globin genes, respectively) were present. A large marked chromosome, involving chromosome 7, and a Philadelphia chromosome were also seen. These data characterize the K562(S) subline and also indicate that hemin and butyric acid differ in their effects on the expression of embryonal globin genes.

Orbitofrontal cholesterol granuloma.

Cholesterol granuloma of the orbital bones is a rare but readily recognisable condition. It is an osteolytic lesion with a granulomatous reaction surrounding cholesterol crystals, old haemorrhage and a fibrous capsule. There is a male preponderance and it usually occurs in young or middle-aged men. It is treatable with drainage and curettage via an orbitotomy, and craniotomy or wide bone removal is almost never required. Six cases of this condition were reviewed to highlight the typical clinical presentation, computed tomography and magnetic resonance results, and surgical management.

An ultra-high sulfur keratin gene is expressed specifically during hair growth.

To study the regulation of the hair cycle in the mouse, we have isolated and characterized a gene for ultra high sulfur keratin that is expressed specifically during the active hair growth cycle. The gene (gUHSK-704Eco) was isolated as a member of a gene cluster on a recombinant phage with a DNA insert of 18 kb that was isolated by screening a murine genomic library at low stringency with a synthetic oligonucleotide derived from a sheep high sulfur keratin gene (Powell, Nucleic Acids Res. 1983 11, 5327). The murine ultra-high sulfur keratin gene has no intervening sequence; the 558 nucleotide of the coding region specify 186 amino acids, of which 70 (37%) are cysteine. A Cys-Cys-Gln-Pro repeat is found 12 times within the coding region. RNA dot blots show that the ultra-high sulfur keratin gene is expressed during the hair cycle concomitant with the anterior-posterior temporal pattern of the normal murine hair cycle.

Hair-specific keratins: characterization and expression of a mouse type I keratin gene.

A genomic clone for a member of the mouse type I hair keratin protein family has been isolated and analyzed in order to study the regulation of this keratin during the hair growth cycle. The coding sequence is divided into seven exons. The gene structure is typical of keratins in particular and intermediate filaments in general in that the intron-exon borders are not located at the domain borders of the protein. Comparison with a sheep wool keratin gene shows that the splice sites in the two hair keratin genes are found at identical locations relative to the amino acid sequence of the proteins. Similarly, comparison of the promoter areas of these genes shows several areas of nucleotide sequence conservation, including the area around the TATA box and an SV40 core enhancer sequence. In addition, a high degree of sequence identity exists in the fourth intron. In situ hybridization shows that transcripts of this gene are first found in the relatively undifferentiated proximal cortex area in the keratogenous zone of mouse vibrissae.

Iron overload is a risk factor for zygomycosis.

Well-recognized risk factors for zygomycosis include diabetic ketoacidosis, immunocompromise, and deferoxamine therapy for iron or aluminum overload, usually in patients undergoing kidney dialysis. We report a case of fatal nasal-orbital-cerebral zygomycosis in an 82-year-old man with known myelodysplasia and well-controlled diabetes. He was not receiving deferoxamine. Despite radical surgery and amphotericin B therapy, he died; primary hemochromatosis with gross iron overload was found post mortem. Experimental evidence suggests iron overload without deferoxamine therapy may be a risk factor for zygomycosis; the findings in this case would support this hypothesis.

High-sulfur protein gene expression in a transgenic mouse.

We analyzed the effect of minoxidil on hair follicles isolated from transgenic mice. These transgenic animals synthesize the reporter enzyme CAT in their hair follicles only during the active phases of hair growth. The recombinant gene used to generate these mice contained the bacterial enzyme CAT under the control of the promoter from the gene of UHS protein. Studies using in situ hybridization showed that UHS proteins are expressed specifically in the matrix cells of the hair follicle during the terminal stages of hair differentiation. Hence the expression of the UHS proteins is a clear sign of active hair growth. With other in situ hybridization studies we demonstrated that CAT mRNA is expressed in differentiating matrix cells of the hair shaft in a location similar to that in which mRNA encodes UHS proteins. Thus we can use the levels of CAT activity as a measure of hair growth. We have confirmed that expression of the transgene is found in hair that is high in anagen and low in catagen follicles. The usefulness of our model was further demonstrated by showing that minoxidil, a drug that stimulates hair growth, increased the expression of CAT in cultured hair follicles. Thus we have demonstrated that expression of this reporter gene is sensitive, hair specific, and also useful for monitoring effects in cultured hair follicles. Hence these transgenic mice provide a model system for studying the biology of hair growth.

Primary orbital liposarcoma: clinical and computed tomographic features.

Liposarcoma of the orbit is rare. The clinical and radiological characteristics of two cases, of myxoid and pleomorphic types, are reported. In neither case was the histological diagnosis evident before surgery.

A technique for reconstruction of upper lid marginal defects.

BACKGROUND/AIMS: Reconstruction of large full thickness upper lid defects that cannot be closed directly often rely on utilising the lower lid. An example is the Cutler Beard procedure. A one stage technique for repair of large horizontal upper lid defects utilising local posterior and anterior lamella advancement flaps is described and the results reported. METHOD: Eight cases with upper lid defects repaired utilising this technique were reviewed retrospectively. The procedures were carried out by one surgeon. The upper lid lesions were removed under frozen section control. The mean follow up time was 35 months. RESULTS: All patients had a good cosmetic result. One patient had a recurrence of the upper lid lesion. Two patients complained of corneal irritation from lanugo hairs. The technique was modified to prevent this complication. CONCLUSIONS: Large upper lid marginal defects can be readily repaired using the technique described with local advancement flaps with no significant complications.

The EEC syndrome and its ocular manifestations.

The EEC syndrome (ectrodactyly or lobster-claw deformity, ectodermal dysplasia, and cleft lip and palate) is a rare disorder with autosomal dominant inheritance, variable expression, and in some families lack of penetrance. We present the findings in five cases with emphasis on the ocular findings. Lacrimal surgery was performed on three patients with good results in each case. We also report the occurrence of spontaneous corneal perforation in two cases, a complication not previously recognised. The ophthalmic care of these patients must be pursued long-term, as progressive visual impairment may be the most disabling feature of the syndrome.

Orbital malignant peripheral nerve sheath tumours.

We describe three patients with malignant peripheral nerve tumours in the orbit and review the existing literature on these rare lesions.

Primary optic nerve sheath meningioma.

Fifty patients with optic nerve sheath meningiomas have been reviewed with a follow-up of up to 15 years. The median age at onset of their symptoms was 40.0 years. The majority were middle aged females with a slowly progressive lesion. More aggressive lesions were encountered in a younger, predominantly male group of patients with frequent intracranial involvement. Our experience indicates that a more aggressive surgical approach to these lesions is needed to prevent this sequence of events. Meningiomas in older individuals often do not need treatment, though radiotherapy can be beneficial.

Optic nerve glioma and the management of optic nerve tumours in the young.

Thirty-one patients presenting as orbital optic nerve glioma have been reviewed with maximum follow-up of 14 years. Sixteen of these patients have been reported on previously and further follow-up is provided. Sixteen patients had a stable clinical course with little change over a period of up to 13.5 years. Neurofibromatosis was relatively common in this group (11/16). Fifteen patients had progressive enlargement of the tumour; the incidence of neurofibromatosis in this group was low (4/15). Eleven of these patients were explored neurosurgically and the optic nerve totally excised in 10 of them. The proximal cut end was normal in six patients and the chiasm has apparently remained free of tumour in all of them. We suggest a method of management of primary optic nerve tumours, both meningiomas and gliomas, in young patients.

The structural proteins of the autonomous parvovirus feline panleukopenia virus.

Approximately 80% of the genome of feline panleukopenia virus was cloned into the plasmid pBR322. The entire 3943 nucleotide sequence of the cloned portion of FPV was determined. This DNA includes the gene which codes for the structural proteins of the virus. Portions of this gene were expressed in E. coli as fusion proteins with bacterial proteins. Some of the fusion proteins were capable of raising neutralizing antibodies in guinea pigs. Through the use of deletion mapping, monoclonal antibodies, and synthetic peptides, attempts were made to localize the portion of the protein responsible for raising these antibodies.

Extracranial orbital decompression for optic neuropathy in Graves' eye disease.

Optic neuropathy affects a small proportion of patients with Graves' eye disease. It is due to optic nerve compression by enlarged extraocular muscles and can be treated by corticosteroids, irradiation or surgical orbital decompression. The current report evaluates the effectiveness of extracranial orbital decompression performed by one surgeon for optic neuropathy in Graves' eye disease. The records of 21 patients (33 orbits) undergoing extracranial orbital decompression for Graves' optic neuropathy were analysed for changes in visual acuity and colour vision and reduction in proptosis. Visual acuity and colour vision improved in all 33 eyes in the short-term postoperatively (4 weeks), but later deteriorated in 5 eyes (6.6%) of 4 patients (19%). The remainder maintained improved vision for the duration of the follow-up period (mean 22, range 3-54 months). Proptosis decreased by a mean 5.0 mm (range 1-8). Extraocular muscle imbalance and diplopia worsened in 9 21 patients (43%) and improved in 2 21 (9.5%). The patients having medial wall and floor decompressed all had worse diplopia (5 5 ), those with medial and lateral wall worsened in 4 10 cases and improved in 1 10 , and those having all three walls decompressed had no cases of worsening diplopia and 1 6 improved. All patients with symptomatic diplopia achieved binocular single vision in a useful range after one and sometimes two squint procedures. No patient lost vision as a result of the extracranial orbital decompression, but one lost vision in one eye after transfrontal decompression following failed extracranial decompression. Extracranial orbital decompression is effective in improving vision and reducing proptosis in most patients with optic neuropathy in Graves' eye disease, but induces or worsens diplopia in a high proportion of patients. The diplopia is readily correctable, and the change to decompressions that include the lateral wall may reduce the risk of postoperative diplopia.

Orbital neurilemmoma: report of seven cases.

Neurilemmoma (schwannoma) has a predilection for the head and neck, especially the eighth cranial nerve in the cerebellopontine angle. It rarely occurs in the orbit, representing only 1% of orbital tumours. We report seven cases. The nerve of origin was identifiable in four cases. Two occurred within the inferior oblique muscle. Five were treated successfully by anterior or lateral orbitotomy without craniotomy and two required a combined cranio-orbitotomy. The majority of orbital neurilemmomas occur as discrete intraorbital lesions without intracranial extension and can be safely removed via orbitotomy alone.

Ultrasonic arrays for monitoring cracks in an industrial plant at high temperatures.

A piezoelectric linear array structure has been designed to operate at temperatures up to 400 degrees C for nondestructive testing of steel components of a hot industrial plant. It is intended that these arrays be fixed permanently to the test subject so that known defects can be monitored by comparing measurements taken over a period of time without needing to shut down the plant. The arrays are used in pairs: the transmitter is a phased array producing a variable angle steered beam, and a second array is used for receiving. The defect can be identified from a series of scans collected from individual elements of the second array. A simple monolithic array structure was used, based on a single crystal of lithium niobate and operating in the frequency range 3 to 5 MHz. Prototype devices have 64 elements on a 0.5 mm pitch. Simulated defects in steel blocks have been scanned at high temperatures to illustrate the arrays' capability for nondestructive testing. The results suggest an accuracy better than 1 mm in finding the location of crack tips.