UIC Eye Pathology

Prognostic Significance

The presence of loops and networks in tissue sections of primary uveal and cutaneous melanomas are associated with an adverse outcome as an independent prognostic factor. There is also evidence that other patterns such as arcs with branching and cross-linking parallel structures are associated with death from metastatic melanoma. These patterns are also found commonly in sites of metastatic disease.

Primary Uveal Melanoma: Networks (PAS without hematoxylin, original magnification X10)

Suggested References - Uveal Melanoma:

Folberg R, et al. The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology 1993;100:1389-1398.

Sakomoto T, et al. Histologic findings and prognosis of uveal malignant melanoma in Japanese patients. Am J Ophthalmol 1996;121:276-283.

McLean IW, et al. Uveal melanoma: comparison of the prognostic value of fibrovascular loops, mean of the ten largest nucleoli, cell type and tumor size. Ophthalmology 1997;104:777-780.

Seregard S, et al. Prognostic accuracy of the mean of the largest nucleoli, vascular patterns, and PC-10 in posterior uveal melanoma. Ophthalmology 1998;105:485-491.

Rummelt V, et al. Microcirculation architecture of metastases from primary ciliary body and choroidal melanomas. Am J Ophthalmol 1998;126:303-305.

Mäkitie T, et al. Microvascular loops and networks as prognostic indicators in choroidal and ciliary body melanomas. J. Natl Cancer Inst 1999;91:359-367.

Suggested References - Cutaneous Melanoma:

Warso MA, et al. Prognostic significance of periodic acid-Schiff-positive patterns in primary cutaneous melanoma. Clin Cancer Res 2001;7:473-477.

Thies A, et al. PAS-positive loops and networks as a prognostic indicator in cutaneous malignant melanoma. J Pathol 2001;195:537-542.

Parenthetical historic note. Examination of some of the titles of the papers in the references posted above may generate some confusion. In the early 1990s, we did not understand the histogenesis of the extravascular matrix patterns and assumed that they represented a type of vessel that had been remodeled by the tumor into unusual topological configurations. Following studies in the late 1990s, it became clear that the looping extravascular matrix patterns were not a host response but were rather formed by a population of aggressive tumor cells, independent of participation by fibroblasts and endothelial cells. Ultrastructural studies performed in the last three years have confirmed that the looping patterns of prognostic significance in melanomas are extravascular - outside the blood vessel circulation.

The patterns, rich in laminin, are easily detectable in tissue sections using the periodic acid-Schiff (PAS) stain, omitting counterstaining with hematoxylin. When this stain is viewed with a green filter, the PAS-positive patterns stand out vividly from the rest of the tumor tissue. The PAS stain is not specific but has been shown to be more convenient and specific than laminin for the purposes of general screening.

Suggested References:

Folberg R, et al. The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study. Hum Pathol 1991;23:1298-1305.

Thies A, et al. PAS-positive loops and networks as a prognostic indicator in cutaneous malignant melanoma. J Pathol 2001;195:537-542.