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PubMed1995

Estrogen and progesterone receptor analysis in ocular melanomas.

BACKGROUND: It has been suggested that pregnancy may promote metastases in melanoma and that the contraceptive pill may be an etiologic factor. The purpose of this study is to determine if uveal or conjunctival melanomas express estrogen or progesterone receptors. METHODS: Twenty-seven choroidal and five conjunctival melanomas were investigated. Immunohistochemistry was performed using the antibodies ER-D5, which recognizes heat-shock protein 27 (formerly called the estrogen receptor-associated cytoplasmic antigen); ER-1D5, which recognizes the estrogen receptor; and PgR, which recognizes the progesterone receptor. RESULTS: Most of the conjunctival and uveal melanomas stained strongly for heat-shock protein 27 but none of the tumors showed positive nuclear staining for either the estrogen or the progesterone receptor. CONCLUSIONS: No evidence was found for either estrogen receptor or progesterone receptor expression in choroidal or conjunctival melanomas. Based on the literature, there is little evidence for these hormones having a role in the development or progression of these tumors.

Adult↗
PubMed1998

Conjunctival amelanotic malignant melanoma arising in primary acquired melanosis sine pigmento.

BACKGROUND: The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. METHODS: Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. STUDY DESIGN: Case report. RESULTS: Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. CONCLUSIONS: Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.

Antigens, Neoplasm↗
PubMed2000

Immunohistochemical diagnosis of malignant melanoma of the conjunctiva and uvea: comparison of the novel antibody against melan-A with S100 protein and HMB-45.

A novel antibody A103, which recognizes melan-A/MART-1, has been found to be more sensitive than the antibody HMB-45, which recognizes gp100, in melanocytic lesions of the skin and might therefore also be useful in the diagnosis of uveal and conjunctival melanocytic lesions. In this study we compared the staining characteristics of anti-melan-A, anti-S100 protein and HMB-45 in 13 conjunctival, 11 iris and 37 ciliary and choroidal malignant melanomas. The ciliary and choroidal melanomas comprised 13 spindle cell (10 spindle B and three spindle A), 14 mixed cell and 10 epithelioid cell tumours. In the conjunctival melanomas the diagnostic sensitivity was 100% for anti-S100 and anti-melan-A and 85% for HMB-45. In the iris melanomas the sensitivity was 100% for anti-S100 and anti-melan-A and 55% for HMB-45. A high staining intensity of anti-melan-A was particularly noticed in iris melanomas. In the choroidal malignant melanomas, the spindle cell and mixed cell types showed a sensitivity of only 69-79% with all three antibodies. In the epithelioid cell type the sensitivity was 80% for anti-S100 and 100% for HMB-45 and anti-melan-A. In conclusion, anti-melan-A was found to be a useful addition to antibody panels for ocular melanocytic lesions. Anti-melan-A has a higher sensitivity than HMB-45 in conjunctival and iris melanomas, but the sensitivity is similar to HMB-45 in choroidal melanomas. Anti-melan-A stains in a very similar pattern to anti-S100, but the staining intensity of anti-melan-A is higher than that of anti-S100 in iris melanoma.

Antibodies, Monoclonal↗
PubMed1986

Ocular findings in patients with dysplastic nevus syndrome.

Ninety-two patients with biopsy-proven dysplastic nevus syndrome were evaluated ophthalmologically and compared to a non-dysplastic nevus syndrome control population. A statistically significant increase in the percentage of dysplastic nevus syndrome patients versus controls harboring conjunctival nevi (9.78% vs. 1.85%), iris nevi (31.52% vs. 12.96%), and choroidal nevi (18.48% vs. 4.63%) was found. Although not statistically significant, the number of iris nevi encountered per patient was greater for the dysplastic nevus syndrome group. All dysplastic nevus syndrome patients and their families should be evaluated ophthalmologically, with special attention being given to dilated indirect ophthalmoscopy.

Adolescent↗
PubMed1985

Assessment of immunological techniques in the diagnosis and prognosis of ocular malignant melanoma.

Tests of cell mediated immunity (one and two stage leucocyte migration inhibition assays) and humoural immunity (membrane immunofluorescence and serum effects on leucocyte migration) were done with leucocytes and sera from 36 patients with uveal melanoma, five with conjunctival melanoma, 21 with non-malignant ocular disease, and 189 with cutaneous melanoma. Cell mediated reactivity with melanoma extracts and serum reactivity with cultured melanoma cells were significantly more frequent in the melanoma patients, but control donor reactivity was also relatively high. Maximum reactivity was found with cells or serum from those patients in whom, on pathological examination, the intraocular melanoma had penetrated the sclera and in patients with conjunctival melanoma. Maximum separation of melanoma patients from control donors was achieved by consideration of the results of several tests done simultaneously. These immunopathological studies were made during the period from 1972 to 1978. At follow-up in 1983 four of the five patients suffering from conjunctival melanoma had died from metastases, and 10 of the 36 with uveal melanoma had died from metastatic disease. The immunological reactions, while of some value in separating melanoma patients from those without melanoma, did not predict whether a particular patient with uveal melanoma would die of metastatic disease or would survive.

Antibody Formation↗
PubMed1985

Unilateral eyelid, conjunctival, and choroidal tumours as initial presentation of diffuse large-cell lymphoma.

Simultaneous ipsilateral eyelid, conjunctival, and choroidal tumours developed in an otherwise healthy man. Biopsy of the eyelid mass led to the diagnosis of large-cell lymphoma. Further examination revealed systemic lymphoma. Although the ocular and adnexal lesions responded to systemic chemotherapy, additional skin tumours later developed. Large-cell lymphoma (also called reticulum cell sarcoma and histiocytic lymphoma) is becoming increasingly recognised for its ophthalmic manifestations. The clinical signs, diagnostic investigations, and treatment of this disease are discussed.

Aged↗
PubMed1995

Primary and secondary orbital melanomas: a clinical and prognostic study.

The clinical, radiologic, and histologic features of 14 cases of orbital melanoma are reviewed. Two cases were presumed to be primary orbital melanomas because no primary pigmented lesion was found in the globe, conjunctiva, or skin. Five cases originated from a conjunctival melanoma, one case from an eyelid cutaneous melanoma, and the remaining six patients had extrascleral extension of a choroidal melanoma. Four patients at the time of first diagnosis already had extraorbital metastases (one patient with extrascleral extension of a choroidal melanoma also had a metastasis to the opposite orbit). The median time interval between diagnosis and metastasis was 14 months. Patients without metastatic disease received radical surgery (partial or total orbital exenteration, in addition to regional lymph node resection if indicated) or conservative treatment (tumor excision plus chemotherapy and interferon). Log-rank test showed an equally poor prognosis for both groups (median time to metastasis was, respectively, 19.5 and 8 months), with no statistically significant difference between the two groups. The authors' reconstructive techniques (dermis-fat grafting and transplantation of temporalis muscle) following partial- and total orbital exenteration are described.

Adipose Tissue↗
PubMed1993

Significance, specificity, and ultrastructural localization of HMB-45 antigen in pigmented ocular tumors.

PURPOSE: To evaluate the expression of the monoclonal HMB-45 antibody in melanocytic and nonmelanocytic ocular tumors and seek "activated" cellular subpopulations in an attempt to distinguish between benign and malignant melanocytes, to compare HMB-45 and S100 activity, and to determine the specificity of this tumor marker for melanocytic ocular lesions. METHODS: Immunohistologic investigations were performed with paraffin-embedded tissue of 10 acquired conjunctival melanoses, 19 conjunctival nevi, 34 conjunctival melanomas, 69 uveal melanomas, 20 basal cell carcinomas of the lid, 20 cystic dermoids, 15 hemangiomas of the lid, 20 conjunctival papillomas, 20 squamous cell carcinomas, 20 pterygia, 11 sebaceous gland carcinomas, 10 retinoblastomas, and 5 choroidal metastatic carcinomas. The avidin-biotin peroxidase technique and monoclonal HMB-45 antibody were used. The distribution of S100 protein was studied in the melanocytic tumors for comparison. To localize the HMB-45 antigen, lowicryl-embedded tissue of uveal melanomas was investigated immunoelectron microscopically. RESULTS: More than 95% of the conjunctival and choroidal melanomas expressed the HMB-45 antigen, while S100 was found in all melanomas of the conjunctiva and in 91% of the uveal melanomas. In benign melanocytic lesions of the conjunctiva (nevi and melanocytes), especially the intraepithelial and junctional components stained with HMB-45, and at the site of tumor invasion, infiltrating cells showed increased HMB-45 reactivity. On the whole, HMB-45 antigen was less evenly distributed in the melanocytic tumors investigated than S100 antigen. All nonmelanocytic ocular tumors revealed no HMB-45 expression. Retinal pigment epithelium and tumor-free choroid were negative for HMB-45. The HMB-45 antigen was immunoelectron microscopically found in melanosomes at stages II and III. CONCLUSION: HMB-45 immunohistology helps in distinguishing melanocytic from nonmelanocytic ocular tumors and often clarifies the front of tumor invasion. The stronger HMB-45 reactivity probably reflects melanocytic activation, but a sharp line between benign and malignant melanocytes cannot be drawn.

Adult↗
PubMed1994

Immunolocalization of integrins in the human retina.

PURPOSE: Integrins are cell surface proteins that participate in interactions between cells and with extracellular matrix. Binding of integrins to their ligands influences cell activities including proliferation, migration, and differentiation. Expression of integrin subunits from three different subfamilies were examined in human retina. METHODS: Integrins were detected in frozen sections of two human retinas with an avidin-biotin-complex immunohistochemical technique, using nine different monoclonal antibodies specific for alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, beta 1, beta 2, and beta 3. One retina was from a patient who had conjunctival squamous cell carcinoma, and the other was from uninvolved regions of an eye with a choroidal melanoma. RESULTS: All integrins tested were detectable in consistent patterns in two retinas. All except alpha 2 and alpha 4 were stained vibrantly in retinal and choroidal vessels. All alpha subunit staining of vessels showed overlap or close proximity to beta 1 staining. In addition to vessels, beta 1 was also present in the internal limiting membrane; alpha 2, alpha 3, alpha 4, alpha 5, and beta 2 were all found throughout much of the neural retina, albeit with distinctive staining patterns. Other than in association with vessels, alpha 6 and alpha v were not detected in neural retina, and beta 3 was only weakly detected in the nerve fiber layer; alpha 4 and beta 2 were expressed in the retinal pigment epithelium; beta 1 and beta 2 were strongly expressed in drusen present in one of the eyes. CONCLUSION: Nine integrin subunits have been found to have unique distributions in adult human retina. An understanding of the distribution in normal retina can serve as a useful contrast to patterns of staining associated with retinal diseases.

Antibodies, Monoclonal↗
PubMed2006

Increased Ki-67 proliferative index and absence of P16INK4 in CIN-HPV related pathogenic pathways different from cervical squamous intraepithelial lesion.

BACKGROUND/AIM: It is generally assumed that similar pathways are involved in human papillomavirus (HPV) induced pathogenesis of cervical squamous intraepithelial lesions (SILs) and cancers and a subset of conjunctival intraepithelial neoplasm (CIN)-that the malignancies or pre-cancerous lesions arise through HPV oncoproteins E6 and E7, which disrupt the pathways of p53 and the product of the retinoblastoma (Rb) gene and, in turn, increase the protein product of gene p16INK4 through the mechanism of positive feedback. Several cell cycle molecules are detected to test this hypothesis. METHODS: Nine cases of CIN and eight non-CIN cases were analysed for the expression of Ki-67, pRb, p53, and p16INK4 via immunohistochemistry. Nine cases of cervical high grade squamous intraepithelial lesion (HSIL), and 10 cases of cervical low grade squamous intraepithelial lesion (LSIL) were included for stain control of p16INK4a, and comparison of p16INK4a expression to CIN cases. A nested polymerase chain reaction and a genechip HPV typing were used to detect HPV infection and types in the CIN and non-CIN samples RESULTS: HPV positivity was demonstrated in all of the CIN lesions but in none of the non-CIN lesions. The Ki-67 proliferative index (Ki-67 PI) was statistically higher in the CIN group than the non-CIN group; however, there were no differences of expression of pRb and p53 between the two groups and no expression of p16INK4 in all cases. All nine cases of HSIL, and seven out of 10 cases of LSIL used for stain control were immunoreactive for p16INK4a. There were statistically significant differences in overexpression of p16INK4a between the CINs and SILs CONCLUSIONS: The Ki-67 proliferative index may be a sensitive marker for CIN lesions and these results, with significant differences in overexpression of p16INK4a between CINs and SILs, may provide new evidence that HPV related mucosal dysplasia in different anatomical locations may lead to dissimilar molecular pathways.

Adolescent↗
PubMed2000

Lack of CD95/FAS gene somatic mutations in extranodal, nodal and splenic marginal zone B cell lymphomas.

Germline CD95 (also known as FAS, APT1 and APO1) gene mutations have been associated with benign lymphoproliferative diseases and autoimmune processes. Somatic mutations have been reported in human tumours, including lymphomas. Since marginal zone B cell lymphomas usually arise in a background of chronic inflammation, often of autoimmune origin, we searched for CD95 gene mutations in an unselected series of marginal zone B cell lymphomas. The CD95/FAS full coding region, comprising exon-intron junctions, was amplified from genomic DNA by polymerase chain reaction (PCR) in 10 separate reactions. PCR products were analysed by single-strand conformation polymorphism (SSCP) and visualised by silver staining. Bands exhibiting an altered electrophoretic mobility were sequenced. Twenty-seven cases of marginal zone B cell lymphomas of whom fresh or frozen tumour material was available (18 extranodal, five splenic and four nodal) were studied. Previously described silent polymorphisms in exons 7 (C836T) and 3 (T416C) were detected in 42% and in 19% of the cases, respectively. One silent T-to-A substitution at bp 431, within exon 3, was found in one case. Our results did not reveal the presence of CD95 somatic mutations in unselected cases of marginal zone B cell lymphomas. On the basis of our data, we cannot rule out that other genes coding for proteins involved in the CD95-induced apoptotic pathway might be altered. However, this pathway does not seem to play an important role in the pathogenesis of these lymphoma subtypes.

Antigens, Neoplasm↗
PubMed2000

Secondary orbital melanomas: analysis of 15 cases.

Orbital melanomas comprise a heterogeneous group of pigmented tumours originating from melanocytes of the ophthalmic tissues, or represent distant metastases of cutaneous melanomas to the orbit. They can be classified into primary and secondary orbital melanomas. Whereas primary orbital melanomas are extremely rare, secondary orbital melanomas are seen more often and usually represent massive extrascleral extensions of uveal melanomas. Their diagnosis is difficult and controversy exists both about the treatment policy and regarding the prognosis. In an effort to clarify some of the aspects of the biological behaviour of these intriguing lesions, we retrospectively reviewed all orbital melanomas treated in our departments during the last eight years. The records of 15 patients with massive secondary orbital melanomas treated surgically were reviewed and analysed. Eleven of the patients were female and four were male. The mean age at the time of surgery was 68 years. Presenting features included unilateral orbital mass, often with painless proptosis, conjuctival bleeding, acute glaucoma crisis, decreased visual acuity and intermittent diplopia. The site of origin was the uveal tract in nine cases, the conjunctiva in three, the eyelids in two and the skin of the lower extremity in one patient. All patients were treated surgically with various types of orbital exenteration. Additional treatment included radiotherapy and chemotherapy. Two patients died from intracranial extension of the disease and 10 died from distant metastases. Three patients are alive with no evidence of disease. The longest survival was 33 months and the mean survival was 16.6 months. Early diagnosis and proper management of ocular melanoma prevents orbital extension and prolongs patient survival. Surgical treatment of secondary orbital melanoma with or without adjuvant radiotherapy and/or chemotherapy does not seem to improve patient survival when compared with conservative treatment used in other reports. However, orbital exenteration is effective for local control of the disease.

Aged↗
PubMed1991

[Distribution of melanoma-associated antigens (HMB 45 and S 100) in benign and malignant melanocytic tumors of the conjunctiva].

The reactivity of the monoclonal antibody HMB 45 was evaluated in melanocytic tumors of the conjunctiva. Among these are 10 acquired melanoses, 19 nevi and 34 melanomas. Results were compared with the presence of the S 100 antigen. Especially the intraepithelial and junctional components of primarily benign lesions were stained with HMB 45. Within malignant melanoma this antibody reacts with melanocytes in the epithelial, junctional and subepithelial areas. The polyclonal antibody S 100 stains all melanocytes in pigmented lesions of the conjunctiva. Intraepithelial or subepithelial malignant infiltrating tumor cells show very intense staining with HMB 45. HMB 45 has therefore high specificity for stimulated melanocytes, but it does not distinguish benign and malignant proliferating melanocytic cells.

Antibodies, Monoclonal↗
PubMed2003

Chapter 9: Role of mucosal human papillomavirus in nongenital cancers.

Established associations between human papillomavirus (HPV) and lower genital tract cancers provide a framework from which to evaluate a possible pathogenic role for the virus in cancers at nongenital sites. Proposed associations must fit coherently within the context of our current knowledge of the epidemiology and biology of HPV. In this article, insights obtained from studies of the etiologic link between mucosal-type HPV infection and four specific human cancers are described briefly. Specific characteristics, shared among cancers caused by HPV, are then used by extrapolation to discuss possible associations between certain other nongenital cancers and mucosal HPV infections in a manner intended to supplement, and in no way to supplant, the classic Hill criteria for causal inference.

Antibodies, Viral↗
PubMed2001

Typical ocular findings in a patient with multiple endocrine neoplasia type 2b syndrome.

BACKGROUND: Multiple endocrine neoplasia (MEN) type 2b syndrome is accompanied by typical ocular findings; however, the disease is often only diagnosed at an advanced stage by symptoms of C-cell carcinoma or pheochromocytoma and is then fatal in most cases. Therefore, the importance of ophthalmic assessment in making the diagnosis has to be stressed. METHODS: The history and ocular findings of a patient with MEN 2b syndrome are described, and a brief overview of the syndrome is given. RESULTS: Slit-lamp examination showed extremely thickened corneal nerves as well as multiple small plexiform and nodular subconjunctival tumors. Both eyes also displayed thickened upper and lower eyelids. A molecular genetic study of the RET proto-oncogene showed a heterozygous ATG to ACG mutation in codon 918 of exon 16. CONCLUSION: Greatly thickened corneal nerves and subconjunctival tumors may be the first hint of MEN 2b. Whenever greatly thickened corneal nerves are detected, MEN 2b must be ruled out.

Adrenal Gland Neoplasms↗
PubMed1983

Pigmented squamous cell carcinoma of the conjunctiva. A clinicopathologic ultrastructural study.

The clinical and morphologic features of a pigmented squamous cell carcinoma of the bulbar conjunctiva in a 57-year-old black man are reported. The tumor resembled the more usual epibulbar squamous cell carcinoma but had many melanin containing cells within it. Transmission electron microscopy disclosed melanosomes within squamous epithelium, melanocytes, and macrophages. The only cells within the tumor with morphologic features of a malignant neoplasm were squamous in type. The literature on this rare conjunctival tumor, which has a good prognosis following complete excision, is reviewed. Pigmented squamous cell carcinomas need to be distinguished from the more common nodular melanomas, which have a more ominous outlook.

Carcinoma, Squamous Cell↗
PubMed2000

The epidemiology of acquired immunodeficiency syndrome malignancies.

The acquired immunodeficiency syndrome (AIDS) results in an extraordinary increase in the risk of two malignancies: Kaposi's sarcoma (KS; relative risk [RR], >10,000) and B-cell non-Hodgkin's lymphoma (NHL; RR, >100). KS appears to result from uncontrolled expression of latency genes of human herpes virus-8 (HHV-8). KS is exquisitely sensitive to immune deficiency, and its incidence has declined during the late 1990s with the advent of highly active antiretroviral therapy (HAART) against human immunodeficiency virus (HIV). The risk of NHL is highest with high-grade histologies, and the incidence has declined only slightly with HAART. The risk of KS and NHL is decreased for people with the CCRS delta32 polymorphism, and NHL risk is increased with the SDFI-3'A polymorphism. Children with AIDS have a similar pattern of risk, but also have a high risk of leiomyosarcoma (RR, approximately 10,000). AIDS-related immune deficiency also increases the risk of Hodgkin's disease (RR, 8), probably multiple myeloma (RR, 5), and possibly other tumors in adults. Although the occurrence of cervical cancer (RR, 3) and anal cancer (RR, 30) is excessive among persons with AIDS, most or all of this excess results from sexually acquired human papillomavirus (HPV) infection and not from immune deficiency. Future efforts need to focus on understanding how the immune perturbation of AIDS results in a limited spectrum of tumors and most urgently on controlling the underlying HIV epidemic.

Acquired Immunodeficiency Syndrome↗