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Modified responses to PGE2 in polyamine biosynthesis by T lymphocytes of gastric- and conjunctiva basal cell-carcinoma patients.

The response to Prostaglandin (PG) E2 of T cells from gastric carcinoma (GC)- and conjunctiva-basal cell carcinoma (conjunctiva-BCC)-bearing patients has been studied in relation to polyamine metabolism. Polyamines are crucial co-factors in cell growth as well as differentiation and many works report that lymphocyte spermine (SP), spermidine (SPD) and putrescine (PUT) levels may be related to tumor proliferation. The present work aims to detect the basal and PGE2 induced concentrations of these polyamines and cAMP, ornithine decarboxylase (ODC), spermine N1-acetyltransferase (SAT) activities of T lymphocytes drawn from patients suffering from GC and conjunctiva-BCC since many carcinomas are characterized by high levels of PGE2. Data obtained from lymphocytes of neoplastic subjects were compared with those derived from PGE2-treated control lymphocytes. Results highlight a very significant increase of all the polyamine metabolites in PGE2-treated T cells from neoplastic patients in respect to the untreated and PGE2-treated control lymphocytes. Therefore, it is conceivable that the PGE2 content increase, often occurring during the epithelial tumour development, may contribute, through enhancement of polyamine metabolism, to tumor progression.

Acetyltransferases↗

Pharmacologic inhibition of immediate hypersensitivity in the guinea pig conjunctiva.

The release of histamine and other mediators from an immediate hypersensitivity reaction is energy dependent and cyclic AMP dependent. Drugs which inhibit the active secretion of mediators, or which may change cyclic AMP are effective in inhibiting mediator release. We used a model of Type I (immediate) hypersensitivity in the conjunctiva of guinea pigs sensitized to normal rabbit serum to test the efficacy of 2-deoxy-D-glucose or a combination of isoproterenol and diethylcarbamazine in inhibiting conjunctival hypersensitivity. After topical challenge with rabbit serum, edema was evaluated in five areas of the guinea pig conjunctiva. Controls were compared to conjunctiva pretreated with 2-deoxy-D-glucose or isoproterenol and diethylcarbamazine. Pretreatment with 2-deoxy-D-glucose or a combination of isoproterenol and diethylcarbamazine was found to inhibit the immediate hypersensitivity reaction.

Animals↗

TP53 mutations in squamous-cell carcinomas of the conjunctiva: evidence for UV-induced mutagenesis.

Squamous cell carcinoma of the conjunctiva is associated with sun exposure and often occurs in HIV-positive individuals. We have analysed TP53 mutations in 21 cases of squamous cell carcinoma and 22 controls with benign conjunctival lesions from a region (Uganda, Africa) with a high prevalence of heavy sun exposure and HIV infection. TP53 mutations were detected in 11 cases (52%) and 3 controls (14%). Seven of the mutations (6 in cases and 1 in controls) were CC-->TT transitions, a molecular signature of mutagenesis by solar UV rays. A similar prevalence (56%) of TP53 mutations was found in 18 squamous cell carcinoma cases positive for epidermodysplasia verruciformis human papillomavirus types. The prevalence of CC-->TT transitions reported here is the highest observed in any cancer type and matches that of skin cancers in subjects with xeroderma pigmentosum, an inherited disease with hypersensitivity to UV damage. These results confirm at the molecular level the causal role of solar UV rays in the aetiology of squamous cell carcinoma of the conjunctiva and suggest that infection with epidermodysplasia verruciformis types of human papillomavirus may act as a cofactor to increase the sensitivity of conjunctiva cells to UV-induced mutagenesis.

Adult↗

Multifocal squamous cell carcinoma of the conjunctiva with intraocular penetration in a patient with AIDS.

PURPOSE: To describe the clinical findings and to study the histopathology of conjunctival masses in a patient with HIV infection. METHODS: A case report. RESULTS: The histopathology from a 38-year-old Thai female patient who presented with visual loss on the left eye was studied. She had been diagnosed with AIDS 3 years before and was treated with highly active antiretroviral therapy and anti-tuberculous drugs for 1 year. The left eye was blind and showed 2 separate whitish masses on the bulbar conjunctiva in adjacent to the inferomedial limbus. Multiple nodules under the conjunctiva were seen inferiorly. Computerized tomography of the orbit revealed slight thickening of the left lower eyelid but could not show any globe involvement. The patient underwent orbital exenteration. Gross pathology showed multiple areas of the tumor. Histopathology revealed dysplastic squamous epithelium invading into the substantia propria of the conjunctiva with intraocular penetration. The anterior surface of the iris was filled with tumor cells containing keratin pearls. CONCLUSION: Squamous cell carcinoma can be multifocal and aggressive in HIV-infected patients. Rapid progression to intraocular penetration can be observed.

Acquired Immunodeficiency Syndrome↗

Short-term mitomycin C followed by long-term interferon alpha2beta for conjunctiva-cornea intraepithelial neoplasia.

PURPOSE: To report a case of extensive conjunctiva-cornea intraepithelial neoplasia (CIN) treated topically with mitomycin C (MMC) and interferon (INF)-alpha2beta without surgical resection. METHODS: Case report. RESULTS: : An 82-year-old woman showed an extensive gelatinous red mass in the bulbar conjunctiva with invasion into the caruncle, inferior fornix, and tarsal conjunctiva and extending for 270 degrees of the corneal surface. A diagnosis of CIN was made by surgical biopsy. Surgical excision with safety margins carried the risk of limbal stem cell depletion. A conservative treatment strategy was used with 2 cycles of topical MMC (0.02%), followed by INF-alpha2beta eye drops at a dose of 1 million IU/mL, 4 times a day until tumor disappearance. Total resolution was noted after 75 days of treatment with INF, with no clinical evidence of limbal stem cell deficiency. After 1 year of monitoring, no signs of CIN recurrences were observed. CONCLUSION: MMC (0.02%), followed by INF-alpha2beta (1 million IU/mL) 4 times a day, is an effective treatment against highly extensive CIN, in cases where surgical resection with safety margins is unfeasible.

Administration, Topical↗

Topical mitomycin treatment for primary acquired melanosis of the conjunctiva.

A case of primary acquired melanosis of the conjunctiva primarily treated with topical mitomycin chemotherapy is presented. The patient underwent treatment with one 2-week course of topical mitomycin 0.02% four times daily, followed 4 weeks later by a 2-week course of topical mitomycin 0.04% four times daily, followed by a 3-month course of topical mitomycin 0.02% twice daily. Map biopsies were performed after the initial two courses of mitomycin therapy and 12 months after all courses of mitomycin treatment had been completed. Complete resolution of the conjunctival pigmentation was noted after the final course of treatment. Map biopsies performed at 12 months following completion of treatment showed normal conjunctiva histopathologically. No recurrence of pigmentation was noted in follow-up 26 months after completion of treatment. Topical mitomycin chemotherapy may be a successful primary treatment for primary acquired melanosis of the conjunctiva.

Administration, Topical↗

Malignant fibrous histiocytoma of the conjunctiva.

Malignant fibrous histiocytoma (MFH) of the conjunctiva is an extremely rare tumour, and only three previous cases have been reported. We describe two patients with MFH of the conjunctiva: a 58-year-old white male with epibulbar tumour who had exenteration and is alive after five years' follow-up, and a 3 1/2-year-old African girl with xeroderma pigmentosum and an MFH of her right eye conjunctiva, the first reported case of this association. The characteristics and the methods of diagnosis of MFH are discussed.

Child, Preschool↗

Primary malignant melanoma of the conjunctiva of the upper eyelid. A case report.

BACKGROUND: Malignant melanoma of the conjunctiva is rare. The nomenclature and clinical and pathologic features of cutaneous and conjunctival melanomas are different. CASE: A 62-year-old male presented with a history of slight bleeding of the upper conjunctiva for the previous six months. On clinical examination the ophthalmologist observed a smooth, partly nodular, pigmented lesion on the conjunctiva under the left eyelid, 1.5 cm in diameter. Fine needle aspiration (FNA) biopsy of the mass showed tumor cells dispersed as single cells with eccentric, round nuclei; coarsely granular chromatin; prominent nucleoli; and dense cytoplasm with occasional brownish pigmentation as well as small aggregates of spindle-shaped neoplastic cells with hyperchromatic nuclei and no cytoplasmic pigment. CONCLUSION: FNA cytology is a simple and efficient method of making the diagnosis of malignant melanoma in conjunctival masses. Careful correlation with the clinical history and histologic findings is often necessary for confirmation of the diagnosis.

Biopsy, Needle↗

Orbital exenterations and squamous cell carcinoma of the conjunctiva at Sekuru Kaguvi Eye Unit, Zimbabwe.

OBJECTIVES: The aim of the audit was to determine the common orbital diseases necessitating orbital exenterations at Sekuru Kaguvi Hospital (SKH) between January and December 1999 and recommend ways of reducing the numbers of procedures done annually. DESIGN: Retrospective cross sectional study. SETTING: Department of Surgery, Parirenyatwa Hospital, University of Zimbabwe. SUBJECTS: 23 patients who underwent orbital exenterations at SKH over a one year period. MAIN OUTCOME MEASURE: The nature of orbital tumours requiring orbital exenteration in Zimbabwe. RESULTS: A total of 23 patients underwent orbital exenteration during the period under review. Of the 23 patients, 13 (56.5%) had squamous cell carcinoma (SCCA) of the conjunctiva with orbital extensions, 69% of the 13 patients were females and the mean age of these patients was 37.2 years (interquartile range 28, 48). CONCLUSIONS: People in tropical regions, where there is a high risk of squamous cell carcinoma of the conjunctiva in terms of increased predisposition to solar radiation, high prevalence of HIV and inadequate eye care services, should seek medical attention as soon as they notice a persistent conjunctival growth. Conjunctival tumours should be widely excised and material sent for histology to confirm diagnosis and clarity of excision margins. All patients diagnosed as having SCCA of the conjunctiva should be closely monitored to facilitate early detection of recurrences and institute appropriate treatment.

Adult↗

Combined nevi of the conjunctiva.

OBJECTIVE: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but rarely has been reported in the conjunctiva. METHODS: Conjunctival nevi and melanomas in the files of the University of California at San Francisco Eye Pathology Laboratory from 1984 to 1999 were reviewed for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained. RESULTS: Thirty combined nevi were discovered between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some may favor a clinical diagnosis of melanoma, no lesions in this series were malignant. CONCLUSION: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus, a combination of a nevocytic and a blue nevus, is common and has been overlooked in the past.

Adolescent↗

Combined nevi of the conjunctiva.

PURPOSE: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but has rarely been reported in the conjunctiva. METHODS: Conjunctival nevi and melanomas from the files of the University of California, San Francisco, eye pathology laboratory were reviewed from 1984 to 1999 for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained. RESULTS: Thirty-one combined nevi were discovered during the 15-year period between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of a blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some patients may favor a clinical diagnosis of melanoma, none of the lesions in this series were malignant. CONCLUSION: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus--a combination of a nevocytic and a blue nevus--is common and has been overlooked in the past.

Adolescent↗

Squamous cell carcinoma of the conjunctiva associated with benign mucous membrane pemphigoid.

A 67-year-old white man with benign mucous membrane pemphigoid OU developed, over a period of two months, a slightly pedunculated fleshy mass in the bulbar conjunctiva OS. The mass was excised and found histopathologically to be squamous cell carcinoma of the conjunctiva. The association of benign mucous membrane pemphigoid and squamous cell carcinoma of the conjunctiva has not been previously reported in the English literature to our knowledge. The significance of the simultaneous occurrence of these two conditions is discussed.

Aged↗

Chemical preparation of the eye in ophthalmic surgery. IV. Comparison of povidone-iodine on the conjunctiva with a prophylactic antibiotic.

We previously found that half-strength (5%) povidone-iodine solution significantly reduced the bacterial flora of the conjunctiva. To compare the antibacterial effect of a topical combination antibiotic (Neosporin ophthalmic solution) given three times daily for three days preoperatively with that of half-strength povidone-iodine solution given as part of the preoperative preparation, conjunctival cultures were studied from 35 patients undergoing ocular surgery. When used individually, the antibiotic and povidone-iodine solutions caused a similar and substantial decrease in the number of colonies and species of bacteria cultured. When both drugs were used together, the decrease was even more striking, making 83% of the conjunctivae sterile. To minimize bacterial flora before ocular surgery, we recommend that a broad-spectrum topical antibiotic be given for three days preoperatively and that half-strength povidone-iodine solution be used as part of the preoperative preparation.

Anti-Bacterial Agents↗

Alteration of microfibrils in the conjunctiva of patients with exfoliation syndrome.

We electron-microscopically studied 15 specimens of upper limbal conjunctiva obtained from 14 patients with exfoliation syndrome and clinical evidence of glaucoma. Of 15 specimens, four (three patients) contained exfoliation materials in the stroma of the conjunctiva. These exfoliation materials of immature, intermediate, and mature forms were composed of abnormal microfibrils lying adjacent to the fibroblasts and located in close proximity to the elastic and collagen fibers. These observations suggest a sequence of events by which microfibrils develop into exfoliation materials.

Aged↗

The ultrastructural defect in conjunctiva from a case of recessive dystrophic epidermolysis bullosa.

The predominant feature in the several forms of epidermolysis bullosa is the formation of cutaneous bullous lesions arising after minimal mechanical trauma. Ocular involvement has been noted as a complication. To our knowledge to date, only four investigators have correlated clinical eye disease with light microscopic findings. Ultrastructure of the ocular lesions has not been described previously. We present four cases of recessive dystrophic epidermolysis bullosa emphasizing their associated ocular complications. Diagnosis was confirmed by skin biopsy specimen and in one patient by demonstrating light and electron microscopic findings in eyelid skin. This tissue exhibited ultrastructural recessive cutaneous lesions; namely, bullous separation occurring below the basal lamina and absence of anchoring fibrils in both bullous and nonbullous areas. By electron microscopy, the conjunctiva in this patient exhibited an absence of clear anchoring fibrils that were numerous in control tissue. This defect may increase the susceptibility of the conjunctiva to minor mechanical trauma, resulting in the bullous and cicatricial changes seen clinically.

Aged↗

Botryomycosis of limbal conjunctiva with Splendore-Hoeppli phenomenon.

An 84-year-old man complained of irritation of the left eye of several months' duration. He had had several previous surgical procedures including removal of bilateral pterygia and bilateral cataract extraction. Examination of the bulbar conjunctiva on the left eye disclosed a collection of cilia (eyelashes) located adjacent to the limbus at the 11:30-o'clock position. This aggregate of cilia was associated with irregular yellowish deposits 1.5 mm in diameter. The cilia and redundant conjunctival tissues were surgically excised. Histopathologic examination showed a botryomycotic granule surrounded by a prominent acidophilic ring (Splendore-Hoeppli phenomenon). Gram stains demonstrated the presence of microcolonies of gram-positive cocci and gram-negative rods within the granule. We postulate that the entrapment of displaced cilia provided a nidus for the bacterial colonization forming the botryomycotic granule. To our knowledge, botryomycosis of the conjunctiva has not been reported previously.

Aged↗

Eosinophils and mast cell homogeneity of the guinea pig eyelid skin, conjunctiva, and ileum.

Mast cell heterogeneity has been described on the basis of differential staining reactions, light microscopic morphology, anatomic location, degranulation after polyamines, biochemical contents, growth requirements, and reactions to lymphokines. We have demonstrated typical "connective-tissue mast cells" by using anatomic criteria, histological staining reactions, electron microscopy, and reaction to compound 48/80 in the guinea pig conjunctiva, eyelid skin, and ileum. A second, much larger population of cells in the ileal mucosa and the conjunctiva, and rarely in the eyelid skin stained reddish-blue with acid toluidine blue in tissue fixed in ethanol-acetate-lead subacetate (BLA) and with alkaline Giemsa in formaldehyde-fixed tissue, did not stain with ethanolic or acid toluidine blue in formaldehyde-fixed tissue or with alkaline Giemsa in BLA-fixed tissue, and did not degranulate after 48/80 treatment. These are features of the rat intestinal "mucosal mast cells"; however, ultrastructural and light microscopic studies with the orcein Giemsa stain demonstrated these cells in the guinea pig to be eosinophils. Tissue culture, biochemical, and immunological studies indicate the existence of a second type of mast cell (bone-marrow-derived mast cell), ultrastructurally almost indistinguishable from the connective tissue mast cell. Our studies demonstrate only one mast cell type in the guinea pig and support the contention that other forms of mast cells are immature forms or variants of the connective-tissue mast cell.

Animals↗

Plasminogen activator inhibitor type 2 (PAI-2) is present in normal human conjunctiva.

The purpose was to characterize plasminogen activator inhibitor type 2 (PAI-2) expression in normal human conjunctiva in vivo and in vitro. PAI-2 antigen was assayed by immunostaining and immunoblotting of extracts from normal human conjunctival epithelial lysates and conditioned media (CM) of cultured human conjunctival keratinocytes. Immunostaining of normal human conjunctival epithelia revealed that PAI-2 was found consistently in the superficial keratinocytes and, in some biopsies, also in the lower keratinocyte layers. In all cases, PAI-2 was concentrated around the cell periphery. In extracts of conjunctival epithelia and cultured conjunctival keratinocytes, PAI-2 had an apparent molecular weight of 45 kDa, consistent with the non-glycosylated form. The majority of PAI-2, approximately 90%, was cell associated, however, a small percentage of PAI-2 was released into the CM in a linear manner with time. PAI-2 in the conditioned medium had a higher molecular weight, consistent with a glycosylated form. Conjunctival PAI-2 was active, as shown by its ability to complex with a target enzyme, urokinase plasminogen activator (uPA). Although PAI-2 was detectable both in monolayer (i.e., relatively undifferentiated) conjunctival keratinocyte cultures as well as in stratified (i.e., more differentiated) cultures, steady state levels of PAI-2 were greater in the latter. PAI-2 is constitutively expressed by normal human conjunctival epithelial cells. The expression of PAI-2 throughout all epithelial layers in some biopsies of conjunctiva in vivo contrasts with the previously established distribution of PAI-2 in corneal epithelia, where it is present exclusively in the most superficial (i.e. most highly differentiated) cells. The role of PAI-2 in either tissue is unclear. However, we speculate that its distinct distribution in conjunctival versus corneal epithelia underscores inherent differences between these tissues, and may reflect specific functions of this proteinase inhibitor in both conjunctival and corneal epithelial cells.

Biopsy↗