Malignant melanoma of the palpebral conjunctiva in a captive fallow deer.

A case of malignant melanoma in the conjunctiva of the eyelid of a captive 13-yr-old female fallow deer (Dama dama) was studied. The black tumor that protruded to the palpebral conjunctiva of the right lower eyelid consisted of an infiltrative growth of melanin-containing neoplastic cells with marked cytological atypia. The tumor involved the conjunctiva of the right lower eyelid and infiltrated to the conjunctival epithelial layer, but did not reach the palpebral skin. Numerous mitotic figures and lymphatic invasions were observed. This is a very rare case of a malignant melanoma arising from the palpebral conjunctiva in a wild ruminant.     

Oncological principles of surgery in the periorbital region

The aim of this study is to describe the most common malignant periorbital tumours and principles of their surgical treatment. The most common malignant tumours of the eyelids are: basocellular carcinoma, squamocellular carcinoma, sebaceous carcinoma and malignant melanoma. The primary treatment of periorbital tumours is surgery, other methods are cryotherapy or radiotherapy. Malignant tumours of the eyelids are fairly rare. Diagnosis in some of the cases is difficult, since the first signs of the tumours are small changes on the eyelid margin or eyelid skin. Focal loss of the eyelashes could be the first sign of a malignant tumour. General oncological principles are valid also in the surgery of periorbital region. Eyelids have special anatomical structure and their main role is protection of the eyeball. Therefore, early diagnosis and total tumour removal--regardless of the anatomical borders--as well as immediate reconstruction are important in the treatment of eyelid tumours.     

Fine needle aspiration cytology of eyelid tumors

Fine needle aspiration (FNA) biopsy was performed on 19 patients with eyelid masses. Six of the patients also had preauricular/submandibular nodal enlargements aspirated. Histopathologic study was performed in ten of the cases. FNA cytology made the diagnosis of an epithelial malignancy in 17 cases (10 sebaceous carcinomas, 4 poorly differentiated carcinomas, 2 squamous cell carcinomas and 1 malignant melanoma). The diagnostic accuracy of FNA cytology in evaluating eyelid masses was thus 89.4%; there were two false-negative cases. All nodal FNA smears revealed metastases of the respective primary tumors. This study indicated that FNA cytology is a simple and efficient method for making the diagnosis of malignancy in eyelid masses, especially in those patients who are not suitable candidates for surgery. Subsequent nodal metastases and tumor recurrence were detected without difficulty using FNA smears.     

Dermatofibrosarcoma protuberans of the upper eyelid treated with surface mould high-dose-rate brachytherapy

Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell tumor, comprising less than 0.1% of all malignant neoplasms. The trunk is the most commonly affected area, followed by the extremities and the head and neck. Of the latter cases, involvement of the periorbital area has been infrequently reported. Surgery is the cornerstone of treatment but is associated with a high rate of recurrence if margins remain close or positive. This rate has been shown to be considerably decreased by the use of adjuvant radiotherapy. However, most reported cases utilize external beam radiation therapy (EBRT ) in the treatment of DFSP, including those with primary periorbital locations. We report a case of a 40-year-old male, presenting with a small nodule on the right upper eyelid, diagnosed as DFSP with positive margins post-surgery and treated with adjuvant customized surface mould high-dose-rate (HDR) brachytherapy in a low-resource setting.     

Active interaction of human A375 melanoma cells with the lymphatics in vivo

We have used the avian chorioallantoic membrane (CAM) to study the interaction of tumor cells with the lymphatics in vivo. The vascular endothelial growth factor-C (VEGF-C) has been shown to be lymphangiogenic. We have therefore grown VEGF-C-expressing human A375 melanoma cells on the CAM. These tumors induced numerous lymphatics at the invasive front, and compressed or destroyed VEGF receptor (R)-3-positive lymphatics were observed within the solid tumors. The lymphatics in the CAM and in the A375 melanomas could also be demonstrated with an antibody against Prox 1, a highly specific marker of lymphatic endothelial cells. Proliferation studies revealed a BrdU labeling index of 11.6% of the lymphatic endothelial cells in the tumors and at their margins. A great number of melanoma cells invaded the lymphatics. Such interactions were not observed with VEGF-C-negative Malme 3 M melanoma cells. Lymphangiogenesis was inhibited to some extent when A375 melanoma cells were transfected with cDNA encoding soluble VEGFR-3 (sflt4), and the BrdU labeling index of the lymphatics in these tumors was 3.9%. Invasion of lymphatics and growth of blood vascular capillaries were not inhibited by the transfection. Therefore, tumor-induced lymphangiogenesis seems to be dependent to some extent on VEGF-C/flt4 interactions, but invasion of lymphatics seems to be a distinct mechanism.     

Merkel cell carcinoma: case report

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma of the skin. Although it is 40 times less common than malignant melanoma, its mortality is much higher compared to melanoma. From 1986 to 2001 there was rapidly increasing incidence in reported cases of MCC, with a tripling in the rate over this 15-year period. The vast majority of MCC presents on sun-exposed skin. The head and neck area is the most common site of tumor occurrence. We present 70-year old female patient with painless red-colored nodule, size 2 x 2 x 2 cm on the dorsal side of mid left forearm. The surgical excision with negative margins was performed, and pathohistological analysis confirmed Merkel cell carcinoma. Sentinel lymph node biopsy was negative. In conclusion, as MCC is a very aggressive rare skin carcinoma with lethal outcome, it should be mandatory to perform biopsies of any suspected skin lesion.     

Lower eyelid reconstruction with the upper eyelid rotation flap

A new technique of lower eyelid reconstruction was developed by using an ipsilateral upper eyelid rotation flap. After resection of a tumor in the lower eyelid, it is possible to replace the defect by a full-thickness upper eyelid rotation flap. Knowledge of exact eyelid anatomy is necessary to perform this kind of operation. In addition to the well-known techniques, the rotation flap constitutes a complete anatomic reconstruction of the lower eyelid with no functional loss of the upper eyelid.     

Effect of human cell malignancy on activity of DNA polymerase ι

An increased level of mutagenesis, partially caused by imbalanced activities of error prone DNA polymerases, is a key symptom of cell malignancy. To clarify the possible role of incorrect DNA polymerase ι (Pol ι) function in increased frequency of mutations in mammalian cells, the activity of this enzyme in extracts of cells of different mouse organs and human eye (melanoma) and eyelid (basal-cell skin carcinoma) tumor cells was studied. Both Mg²⁺, considered as the main activator of the enzyme reaction of in vivo DNA replication, and Mn²⁺, that activates homogeneous Pol ι preparations in experiments in vitro more efficiently compared to all other bivalent cations, were used as cofactors of the DNA polymerase reaction in these experiments. In the presence of Mg²⁺, the enzyme was active only in cell extracts of mouse testicles and brain, whereas in the presence of Mn²⁺ the activity of Pol ι was found in all studied normal mouse organs. It was found that in cell extracts of both types of malignant tumors (basal-cell carcinoma and melanoma) Pol ι activity was observed in the presence of either Mn²⁺ or Mg²⁺. Manganese ions activated Pol ι in both cases, though to a different extent. In the presence of Mn²⁺ the Pol ι activity in the basal-cell carcinoma exceeded 2.5-fold that in control cells (benign tumors from the same eyelid region). In extracts of melanoma cells in the presence of either cation, the level of the enzyme activity was approximately equal to that in extracts of cells of surrounding tumor-free tissues as well as in eyes removed after traumas. The distinctive feature of tissue malignancy (in basal-cell carcinoma and in melanoma) was the change in DNA synthesis revealed as Mn²⁺-activated continuation of DNA synthesis after incorrect incorporation of dG opposite dT in the template by Pol ι. Among cell extracts of different normal mouse organs, only those of testicles exhibited a similar feature. This similarity can be explained by cell division blocking that occurs in all normal cells except in testicles and in malignant cells.     

FHOD1 formin is upregulated in melanomas and modifies proliferation and tumor growth

The functional properties of actin-regulating formin proteins are diverse and in many cases cell-type specific. FHOD1, a formin expressed predominantly in cells of mesenchymal lineage, bundles actin filaments and participates in maintenance of cell shape, migration and cellular protrusions. FHOD1 participates in cancer-associated epithelial to mesenchymal transition (EMT) in oral squamous cell carcinoma and breast cancer. The role of FHOD1 in melanomas has not been characterized. Here, we show that FHOD1 expression is typically strong in cutaneous melanomas and cultured melanoma cells while the expression is low or absent in benign nevi. By using shRNA to knockdown FHOD1 in melanoma cells, we discovered that FHOD1 depleted cells are larger, rounder and have smaller focal adhesions and inferior migratory capacity as compared to control cells. Importantly, we found FHOD1 depleted cells to have reduced colony-forming capacity and attenuated tumor growth in vivo, a finding best explained by the reduced proliferation rate caused by cell cycle arrest. Unexpectedly, FHOD1 depletion did not prevent invasive growth at the tumor margins. These results suggest that FHOD1 participates in key cellular processes that are dysregulated in malignancy, but may not be essential for melanoma cell invasion.     

The evaluation and management of lower eyelid retraction following cosmetic surgery

Lower eyelid retraction is a common complication after cosmetic surgery of the lower eyelids, midface, and the adjacent face. Lower eyelid retraction is defined as the inferior malposition of the lower eyelid margin without eyelid eversion. Lower eyelid retraction presents clinically with scleral show; round, sad-looking eyes; lateral canthal tendon laxity; and symptoms of ocular irritation, including photophobia, excessive tearing, and nocturnal lagophthalmos. These patients frequently require ocular lubricants, including artificial tears and ointments, which often provide only minimal alleviation of their symptoms. The author has observed that lower eyelid retraction is usually accompanied by midface descent. On the basis of surgical observations, the causes of lower eyelid retraction seem to be multifactorial and include scarring between the orbital septum and capsulopalpebral fascia (or lower eyelid retractors), lateral canthal tendon laxity, and midface descent. After describing the causes of lower eyelid retraction, the author presents a system for evaluating patients that can assist the surgeon in choosing the surgical procedure(s) required to correct the lower eyelid malposition. The surgeon must know how to tighten a lax lateral canthal tendon, be familiar with the anatomy of the lower eyelid from conjunctiva to skin side, and know how to surgically elevate the midface. The techniques for correcting lower eyelid retraction are also presented. Appropriate surgery, which is determined on the basis of the preoperative evaluation, has allowed for the correction of these previously difficult-to-treat lower eyelid malpositions with minimal complications.     

Anatomic microstructure of the upper eyelid in the Oriental double eyelid

The anatomic differences in the microstructure of the upper eyelid between the double eyelid and the nondouble eyelid are compared to determine the mechanism of double eyelid formation. Tissue from the upper eyelids of normal adult women was categorized into three groups: in one group, the double eyelid was formed primarily (at birth); in a second group, the double eyelid was formed gradually; and those in a third group had nondouble eyelids. A total of 56 eyelids were studied using electron microscopy and light microscopy. The results indicated that there is a significant difference between the three groups using scanning electron microscopy. In the upper eyelid of the double eyelid, bunched fibers of levator aponeurosis penetrate through orbicularis muscle to fuse with the skin in palpebral sulcus. This structure was not observed in the group with nondouble eyelids. However, when using light microscopy, this disparity was not observed. It was concluded that a fiber-linked structure between eyelid skin and levator aponeurosis is essential for the formation of the double eyelid.     

Initial management of cutaneous malignant melanoma.

Appropriate initial surgical management of primary cutaneous malignant melanoma is important since no effective treatment exists once the tumour metastasizes. The author reviews methods of initial treatment, excisional biopsy with adequate margins being the most common. He also reports results from a questionnaire survey on the type of microstaging used at hospitals across Canada. Two thirds of the pathologists who responded to the questionnaire preferred to use both Clark''s and Breslow''s method of microstaging. As a result, the author believes that the best histopathologic classification to use for predicting outcome has yet to be established.     

Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry

Background  

Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM) is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model.     

A dual role of FGF10 in proliferation and coordinated migration of epithelial leading edge cells during mouse eyelid development

The development of the eyelid requires coordinated cellular processes of proliferation, cell shape changes, migration and cell death. Mutant mice deficient in the fibroblast growth factor 10 (Fgf10) gene exhibit open-eyelids at birth. To elucidate the roles of FGF10 during eyelid formation, we examined the expression pattern of Fgf10 during eyelid formation and the phenotype of Fgf10-null eyelids in detail. Fgf10 is expressed by mesenchymal cells just beneath the protruding epidermal cells of the nascent eyelid. However, Fgf10-null epithelial cells running though the eyelid groove do not exhibit typical cuboid shape or sufficient proliferation. Furthermore, peridermal clumps are not maintained on the eyelid leading edge, and epithelial extension does not occur. At the cellular level, the accumulation of actin fibers is not observed in the mutant epithelial leading edge. The expression of activin/inhibin betaB (ActbetaB/Inhbb) and transforming growth factor alpha (Tgfa), previously reported to be crucial for eyelid development, is down-regulated in the mutant leading edge, while the onset of sonic hedgehog (Shh) expression is delayed on the mutant eyelid margin. Explant cultures of mouse eyelid primordia shows that the open-eyelid phenotype of the mutant is reduced by exogenous FGF10 protein, and that the expression of ActbetaB and Tgfa is ectopically induced in the thickened eyelid epithelium by the FGF10 protein. These results indicate a dual role of FGF10 in mouse eyelid development, for both proliferation and coordinated migration of eyelid epithelial cells by reorganization of the cytoskeleton, through the regulation of activin, TGFalpha and SHH signaling.     

Melanoma Cells Break Down LPA to Establish Local Gradients That Drive Chemotactic Dispersal

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient.     

Early release of third-degree eyelid burns prevents eye injury

Burns to the eyelids occur in more than 20 percent of flame injuries and can lead to ocular damage and even blindness. Burn wound contracture can cause ectropion of the eyelid, resulting in exposure keratitis, corneal ulcers, and conjunctivitis. At our hospital, early eyelid release and grafting has made a significant difference in the long-term outcomes of third-degree eyelid burns; however, the question of just how early eyelid release and grafting should take place is an unresolved issue. Fifty-seven children with third-degree eyelid burns were reviewed; 17 had eyelid release within 7 days of receiving eyelid burns and 40 had a delay in eyelid release of more than 7 days after injury. Analysis was by chi-square with the Yates continuity correction or Fisher's exact test when appropriate. Corneal ulcers developed in 2 of 17 of the early eyelid release of third-degree burns, compared with 25 of 40 delayed releases (p = 0.001), exposure keratitis in 3 of 17 early releases, and 30 of 40 in delayed release (p = 0.000); conjunctivitis was identified in 1 of 17 early releases and 14 of 40 delayed eyelid releases (p = 0.025). Release of eyelid burns within 7 days of injury can prevent the development of exposure keratitis, progressive conjunctivitis, corneal ulceration, and the need for corneal surgery. We suggest that early release and grafting should be the treatment of choice for children and young adults with third-degree burns to the eyelids.     

Elastohydrodynamics of the Eyelid Wiper

This paper presents an elastohydrodynamic model of the human eyelid wiper. Standard lubrication theory is applied to the fluid layer between the eyelid wiper and ocular surface. The role of the lubrication film is to reduce the shear stresses by preventing solid to solid contact between the eyelid wiper and ocular surface. For the lubrication film to be effective, it is required that the orientation of the eyelid wiper changes between the opening and closing phases of a blink. In order to model this, the hydrodynamic model is coupled with an elastic mattress model for the soft tissue of the eyelid wiper and ocular surface. This leads to a one-dimensional non-linear partial differential equation governing the fluid pressure in the lubrication film. In order to solve the differential equation, a loading condition or constraint equation must be specified. The resulting system is then solved numerically. The model allows predictions of the tear film flux from under the upper eyelid, as well as normal and shear stresses acting on the ocular surface. These factors are important in relation to dry eye syndrome, deformation of the cornea and contact lens design. It is found that the pressure and shear stress under the eyelid act across a length of approximately 0.1 mm which is consistent with clinical observations. It order to achieve a flow of tears from under the upper eyelid during a blink, the model requires that the normal force the eyelid applies to the ocular surface during the closing phase of the blink is significantly higher than during the opening phase of the blink. Electronic Supplementary Material The online version of this article () contains supplementary material, which is available to authorized users.     

Transblepharoplasty lower eyelid and midface rejuvenation: part II. Functional applications of midface elevation

Lower eyelid malposition is the cause of many ophthalmologic complaints, including ocular foreign-body sensation, irritation, excessive tearing, and sensitivity to light. The lower eyelid and midface are intimately associated structures. Midface descent frequently occurs in conjunction with lower eyelid laxity and descent. Elevating the lower eyelid and midface back to their normal anatomic positions frequently improves symptoms in these patients. The author has utilized the same techniques frequently used by aesthetic surgeons to elevate the lower eyelid and midface for patients, with improvement or resolution of their ocular complaints. The technique and results are presented.     

Lymphedema of the eyelids

Lymphedema of the eyelids is a relatively rare condition whose main effect is to obstruct vision, and it is unsightly. We present 3 cases in which the edema was treated by excision and skin grafting of the eyelid, with satisfactory functional and cosmetic results. It is suggested that a split-skin graft be used for the upper eyelid and a full-thickenss graft for the lower eyelid. The lower eyelid skin can be "de-fatted" and used as a graft, but in the more severe cases we suggest a postauricular skin graft be used.