Melanoma associated spongiform scleropathy: characterization, biochemical and immunohistochemical studies.
Melanoma associated spongiform scleropathy (MASS) is a non-inflammatory scleral change with a spongiotic morphology seen in association with uveal melanoma. MASS is seen as whitish spindle shaped areas within the sclera that is adjacent to and in contact with a choroidal or ciliary body melanoma. This change can be seen as small scattered lesions in the inner scleral layers or as extensive areas along the whole extent of contact between the tumour and the sclera and involves most of the scleral thickness. MASS changes of different grades of severity were seen in 38% of 363 melanoma eyes investigated. The presence of MASS showed a statistical correlation with age. A significant high incidence of MASS was found in old age groups. This might due to the fact that MASS needs a longer period of contact between the tumour and the sclera to develop. It is also possible that age-related changes of the extracellular matrix might alter its response to melanoma produced factors leading to the development of MASS. The development of MASS and its severity are influenced by the extent of contact between the tumour and the sclera. This is supported by the significant statistical relation between the largest basal diameter of the tumours and the severity of MASS. Statistical correlation was found between MASS and scleral and extrascleral tumour extension. More than 90% of 82 specimens that showed tumour extension were associated with MASS. A biochemical analysis of scleral samples taken from areas with severe MASS showed a significant reduction of the main amino acids of collagen type I, which is the main scleral collagen. The amounts of total scleral proteins were significantly reduced. This scleral protein reduction is associated with an increase in glycosaminoglycans. These findings indicate a collagen degradation process. Immunohistochemical studies were performed to investigate the expression of matrix metalloproteinases (MMPs). In situ hybridization showed a significantly more frequent and more intense expression of MMP-2 by scleral fibroblasts in areas with MASS compared with areas without MASS. This was also seen by immunohistochemical staining. Similar high frequency and intense expression of MMP-2 were seen in tumour infiltrating macrophages. The results of biochemical and immunohistochemical studies indicate a collagen degradation process. This degradation may be the result of the proteolytic enzyme MMP-2 expressed by scleral fibroblasts under the effect of tumour humeral factors and/or tumour infiltrating macrophages. This scleral degradation results in fragmentation of the scleral collagen fibrils. This along with the accumulation of water in the sclera, as a result of the increase in the production of glycosaminoglycans, results in increase of scleral thickness in MASS areas and forms the histopathological picture of MASS. The scleral degradation may facilitate tumour invasion and may explain the statistical relation between MASS and scleral tumour invasion. MASS was found in a few of the eyes that had received pre-enucleation radiation. The possible explanation is that radiation might cause destruction of scleral fibroblasts reducing their ability to produce MMP-2, thus decreasing the development of MASS. No relation between MASS and survival was found. This is probably explained by the fact that the main cause of death due to uveal melanoma is distant metastasis. MASS changes are found to be associated with local tumour invasion but not statistically correlated to survival.
Alyahya
Ghassan Ayish
GA
Eye Pathology section, Institute of Neuroscience and Pharmacology, University of Copenhagen.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012590:Sclera / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D012720:Severity of Illness Index; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology
D020778:Matrix Metalloproteinase 2