"MIND THE GAP" IN IMMUNOHISTOCHEMICAL TECHNIQUES USED IN PATHOLOGY OF PITUITARY ADENOMAS

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.

[1]  G. Kontogeorgos.  Classification and pathology of pituitary tumors , 2005, Endocrine.

[2]  K. Kovacs,et al.  Classification of pituitary adenomas , 2001, Journal of Neuro-Oncology.

[3]  T. Kawase,et al.  Morphological Characterization and Subtyping of Silent Somatotroph Adenomas , 1999, Pituitary.

[4]  K. Kovacs,et al.  Oncocytes in the anterior lobe of the human pituitary gland , 1974, Acta Neuropathologica.

[5]  S. Roy,et al.  Functioning oncocytic adenoma of the pituitary , 2004, Journal of Neuro-Oncology.

[6]  J. Ironside,et al.  Best Practice No 172 , 2003, Journal of clinical pathology.

[7]  Dr. Geoffrey R. Newman,et al.  Resin Microscopy and On-Section Immunocytochemistry , 1993, Springer Lab Manuals.

[8]  Hiroshi Ito,et al.  Immunohistochemical demonstration of oncocytes in nongonadotrophic pituitary adenomas , 1999, Virchows Archiv.

[9]  B. Scheithauer,et al.  The world health organization classification of adenohypophysial neoplasms: A proposed five‐tier scheme , 1996, Cancer.

[10]  F. Brucker-Davis,et al.  Thyrotropin-secreting pituitary tumors. , 1987, Endocrine reviews.

[11]  A. Spada,et al.  In vitro detection of glycoprotein production and secretion by human nonfunctioning pituitary adenomas , 1993, Journal of endocrinological investigation.

[12]  A. Klibanski,et al.  Imbalanced follicle-stimulating hormone beta-subunit hormone biosynthesis in human pituitary adenomas. , 1992, The Journal of clinical endocrinology and metabolism.

[13]  S. Asa,et al.  Functional endocrine pathology , 1991 .

[14]  S. Asa,et al.  Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. , 1989, The American journal of pathology.

[15]  P. Black,et al.  Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. , 1987, The Journal of clinical investigation.

[16]  K. Kovacs,et al.  Clinically silent hypersecretion of growth hormone in patients with pituitary tumors. , 1987, Journal of Neurosurgery.

[17]  P. Black,et al.  Hormone production in clinically nonfunctioning pituitary adenomas. , 1987, Journal of neurosurgery.

[18]  E. Ogata,et al.  A case of pituitary adenoma with possible simultaneous secretion of thyrotropin and follicle-stimulating hormone. , 1982, The Journal of clinical endocrinology and metabolism.

[19]  M. Coculescu,et al.  Hormonal evidence for the dissemination through the cerebrospinal fluid, of secreting cells from invasive pituitary adenomas. , 1981, Endocrinologie.

[20]  S. Hsu,et al.  Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. , 1981, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[21]  N. Halmi,et al.  Prolactin‐secreting pituitary oncocytoma with galactorrhea–amenorrhea syndrome. A histologic, ultrastructural, and immunocytochemical study , 1980, Cancer.

[22]  K. Kovacs,et al.  Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study. , 1980, The American journal of pathology.