Päivi Toivonen

Prognostic Significance of Histopathology of Primary Conjunctival Melanoma in Caucasians

Purpose: To assess histopathologic prognostic factors relative to clinical ones in predicting local recurrence and survival after primary conjunctival melanoma (CM). Methods: 85 patients with CM were identified in Finland between 1967 and 2000, and 70 primary tumors were available for histopathologic study. Time to first recurrence and melanoma-related mortality were analyzed. Results: Absence of epithelioid cells (P = 0.033), smaller mean diameter of the ten largest nucleoli (P = 0.041) and increasing mitotic count (P = 0.042) were associated with shorter time to recurrence. The mean diameter of the ten largest nucleoli, the number of tumor-infiltrating lymphocytes and macrophages, extravascular matrix loops and networks, and microvascular density were unassociated with recurrence. Nonlimbal location (P = 0.001), recurrence (P < 0.001), and increasing tumor thickness (P = 0.007) were associated with mortality. By multivariate Cox regression, a model including recurrence and tumor location fitted best with mortality data. Conclusions: Histopathological factors are not consistently associated with survival in CM. Tumor location, thickness, and recurrence are predictors of mortality from CM.

Infiltrating macrophages in extratumoural tissues after brachytherapy of uveal melanoma

Purpose:  To compare distribution of macrophages in extratumoural ocular tissues in enucleated eyes with irradiated and nonirradiated uveal melanomas to find out how irradiation affects distribution of macrophages so as to gain insight into their potential routes of migration and changes in local inflammatory responses.

Macrophages and microcirculation in regressed and partially regressed irradiated choroidal and ciliary body melanomas.

Purpose. To investigate how tumour-infiltrating macrophages and microcirculation attributes of uveal melanomas regressed after brachytherapy and whether primarily enucleated melanomas differ. Methods. A case-control analysis of 34 matched pairs of irradiated and nonirradiated choroidal and ciliary body melanomas with main outcome variables being area of necrosis, extravascular matrix loops and networks, tumour-infiltrating macrophages in nonnecrotic areas identified with mAb PG-M1 to the CD68 epitope, and microvascular density (MVD) determined by mAb QBEND/10 to the CD34 epitope. Results. Comparison of primarily enucleated eyes to eyes with irradiated, secondarily enucleated melanomas revealed significantly more necrosis (median difference, +9%, P = 0.0012) and lower MVD (median difference, -10 counts/0.313mm 2, P = 0.011) in the latter. In eyes managed with brachytherapy, loops and networks tended to be less frequent (P = 0.077). Number and type of macrophages weresimilarly distributed, being moderate to high in about 95% (P = 0.67) of the matched pairs, and intermediate to dendritic in 79% (P = 0.90). In the irradiated eyes, presence of epithelioid cells and the number and type of macrophages showed no association with microcirculation attributes, whereas in the primarily enucleated tumours, high number of macrophages was associated with high MVD (P < 0.001). Conclusions. This study suggests that regression after brachytherapy reduces MVD. The difference cannot be attributed to different numbers of tumour-infiltrating macrophages and different cell type in nonnecrotic areas of the tumour.

Microvascular loops and networks in uveal melanoma.

Microvascular patterns--three-dimensional architectural arrangements of microvessels and extravascular matrix in uveal melanoma--were discovered when investigators were looking for histopathological features of sufficient size to be imaged clinically. Evidence that these patterns may be formed by tumour cells and that they may be able to conduct plasma and blood as well as discovery of similar elements in other cancers make them of general importance. Of nine different patterns described, closed microvascular loops and networks have been studied most extensively. When cell type, microvascular density and nucleolar size are controlled for, these two patterns independently predict time to metastasis. In addition to visualization in tumour specimens stained with periodic acid-Schiff reagent, they can often be visualized clinically on confocal indocyanine green angiography. The presence of networks is clinically associated with probability of growth of small uveal melanocytic tumours and with the rate of regression of uveal melanoma after brachytherapy. Networks are also associated with development of exudative retinal detachment from uveal melanoma. Histopathological studies show that loops and networks are less common in tumours enucleated after irradiation and that they are frequently repeated in metastases of uveal melanoma. Avenues for immediate future research include detailed elucidation of the histogenesis of microvascular patterns and determination of these patterns in metastatic melanoma to identify new histopathological characteristics for prognostication when clinical metastases have developed.

Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases

Purpose:  This study aimed to investigate the relationship between hepatic metastasis and the mean diameter of the 10 largest nucleoli (MLN) in uveal melanoma.