"Mind the gap" in immunohistochemical techniques used in pathology of pituitary adenomas

Abstract

Pituitary adenomas are fully characterized only by immunohistochemistry. The technical limitations, gaps and peculiarities influence the pathology diagnosis. More and more data shows that clinically nonfunctioning pituitary adenomas could synthesize or secrete hormones or their subunits. The tumor pathology is monomorphous or polymorphous, difficult to differentiate from normal adjacent tissue. Light microscopy (LM) qualitative analysis using basic or special stains can differentiate between tumor and normal tissue and allows elimination of artifacts. Electron microscopy (EM) completes the diagnosis in selected cases. Pituitary adenomas immunohistochemistry was done by LM in 120 cases (84 – clinically nonfunctioning adenomas – NFA and 36 acromegalics with or without PRL secreting adenomas - ACM) using the avidine-biotin complex method. In 26 cases we determined by EM the immunoreactive cells (17 NFA and 9 ACM) using the immunogold method. We observed high tumor immunoreactivity (mono or plurihormonal) in 43/84 (51%) NFA, 13/36 (36%) ACM respectively. Serum excess hormones and tissue immunoreactivity were significantly concordant for prolactin in NFA cases and for GH, in ACM cases (p<0.05). Mute pituitary adenomas have no clinical expression of hormonal products either they produce biologically inactive components or they synthesize but do not secrete hormones in sufficient amounts to increase serum level and to determine a systemic response. A concordance between LM and EM immunoreactivity was observed only for GH in ACM patients group (p<0.05). The differences could be due to dimensions of the samples or the number of granules inside of the cells (sparsely granulated adenomas are negative or low immunoreactive at the LM level). EM evaluation of NFA identified 2 oncocytomas and 4 null cell adenomas. The complete evaluation of pituitary adenomas includ a qualitative and quantitative analysis at the LM level using special methods, validated at the EM level in order to identify clinically mute immunoreactive cells – a possible target for specific drugs therapies in the future.