Type IV collagen immunostaining is a simple, reliable diagnostic tool for distinguishing between adenomatous and normal pituitary glands

Abstract

Context: Pituitary adenomas are clinically diagnosed based on radiologic studies and/or secondary effects of hormone production. Definitive pathologic identification relies on immunohistochemical detection of a clonal population of hormone-producing cells. However, not all adenomas secrete hormones, so performing a battery of stains is inefficient. Reports have shown decreased type IV collagen in the stroma of other epithelial tumors.

Objective: To validate type IV collagen immunohistochemistry as a diagnostic method.

Design: We immunostained 27 adenomas and 19 normal pituitaries. The areas with the sparsest type IV collagen fibers were viewed at 3 magnifications (x10, x20, and x40 objectives), counting 1, 3, or 10 microscopic fields. A field was scored as "traversable" if a path existed from any point on the periphery of the field to a point on the approximately opposite periphery that did not cross any stained fibers. Results were compared with reticulin staining and to the existing diagnosis previously determined by histology, hormone immunostaining, and clinical correlation.

Results: Adenomas have less type IV collagen in their basement membranes, leading to sparser, trabecular staining in neoplasms versus a more rigid meshwork pattern in normal glands. One might envision the stained fibers as maze walls--one can traverse medium-powered fields in an adenoma, but one hits dead ends and gets trapped in those of a normal gland. Finding a single representative x10 field to be traversable was 97.5% sensitive and 96.5% specific for an adenoma. Reticulin staining yielded identical results.

Conclusions: Type IV collagen immunostaining is a simple and reliable method of diagnosing pituitary adenomas.