title: Type IV collagen immunostaining is a simple, reliable diagnostic tool for distinguishing between adenomatous and normal pituitary glands.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pathology, University of Michigan Hospitals and Clinics, Ann Arbor, USA. jjarzembowski@path.wustl.edu
authors.forename: Jason
authors.initials: J
authors.lastname: Jarzembowski
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lloyd
authors.forename: Paul
authors.initials: P
authors.lastname: McKeever
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D024141:Collagen Type IV / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000378:metabolism* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011237:Predictive Value of Tests; D012155:Reticulin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D024141:Collagen Type IV; D012155:Reticulin