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Prolactin-Producing Pituitary Adenoma and Carcinoma with Neuronal Components<197>A Metaplastic Lesion

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Abstract

Recent studies indicate that cells of various epithelial tumors are capable of transformation to neurons. Observing both neurons and neuropil in two prolactin-producing adenohypophyseal tumors, one benign and one malignant, we sought to assess their cellular differentiation, the presence of nerve growth factor receptor, and expression of the dopamine receptor gene using immunocytochemistry, electron microscopy, and in situ hybridization. Light and electron microscopy clearly revealed cells morphologically transitional between adenoma/carcinoma cells and neurons. Large neurons lacked proliferative activity. Neurons in varying number showed immunoreactivity for pituitary hormones including prolactin, growth hormone and alpha subunit in the adenoma and prolactin alone in the carcinoma. The distribution of nerve growth factor receptor staining was similar. In both tumors, in situ hybridization showed mRNAs for prolactin and dopamine receptor within adenohypophyseal cells and neurons. Our results indicate that the occurrence of neurons and neuropil in growth hormone and prolactin-producing pituitary tumors appears to be the result of metaplasia. The process is not limited to benign tumors and may be due to the production of tropic substances by the adenohypophysial cells, which by paracrine/autocrine mechanisms result in transformation of adenoma cells to nerve cells.

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References

  1. Kiyono H. Die histopathologies der hypophyse. Virchows Arch Pathol Anat 1926;259:388–465.

    Google Scholar 

  2. Lach B, Rippstein P, Benoit BG, Staines W. Differentiating neuroblastoma of pituitary gland: neuroblastic transformation of epithelial adenoma cells. J Neurosurg 1996;85:953-960.

    Google Scholar 

  3. Towfighi J, Salam MM, McLendon RE, Powers S, Page RB. Ganglion cell-containing tumors of the pituitary gland. Arch Pathol Lab Med 1996;120:369–377.

    Google Scholar 

  4. Asa SL, Bilbao JM, Kovacs K, Linfoot JA. Hypothalamic neuronal hamartoma associated with pituitary growth hormone cell adenoma and acromegaly. Acta Neuropathol 1980; 52:231–234.

    Google Scholar 

  5. Fischer EG, Morris JH, Kettyle WM. Intrasellar gangliocytoma and sydromes of pituitary hypersecretion. J Neurosurg 1983;59:1071–1075.

    Google Scholar 

  6. Scheithauer BW, Kovacs K, Randall RV, Horvath E, Okazaki H, Laws ER Jr. Hypothalamic neuronal hamartoma and adenohypophysial neuronal choristoma: Their association with growth hormone adenoma of the pituitary gland. J Neuropathol Exp Neurol 1983;42:648–663.

    Google Scholar 

  7. Asa SL, Scheithauer BW, Bilbao JM, Horvath E, Ryan N, Kovacs K, Randall RV, Laws ER Jr, Singer S, Linfoot JA, Thorner MO, Vale W. A case for hypothalamic acromegaly: A clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab 1984;58:796–803.

    Google Scholar 

  8. Bevan JS, Asa SL, Rossi ML, Esiri MM, Adams CBT, Burke CW. Intrasellar gangliocytoma containing gastrin and growth hormone-releasing hormone associated with a growth hormone-secreting pituitary adenoma. Clin Endocrinol 1989;30:213–224.

    Google Scholar 

  9. Kamel OW, Horoupian DS, Silverberg GD. Mixed gangliocytoma-adenoma: A distinct neuroendocrine tumor of the pituitary fossa. Hum Pathol 1989;20:1198–1203.

    Google Scholar 

  10. Li JY, Racadot O, Kujas M, Kouadri M, Peillon F, Racadot J. Immunocytochemistry of four mixed pituitary adenomas and intrasellar gangliocytomas associated with different clinical syndromes: Acromegaly, amenorrhea-galactorrhea, Cushing' disease and isolated tumoral syndrome. Acta Neuropathol 1989;77:320–328.

    Google Scholar 

  11. Slowik F, Fazekas I, Balint K, Gazso L, Pasztor E, Czirjak S, Lapis K. Intrasellar hamartoma associated with pituitary adenoma. Acta Neuropathol 1990;80:328–333.

    Google Scholar 

  12. Burchiel KJ, Shaw CM, Kelly W. A mixed functional microadenoma and ganglioneuroma of the pituitary fossa. J Neurosurg 1983;58:416–420.

    Google Scholar 

  13. Horvath E, Kovacs K, Scheithauer BW, Lloyd RV, Smyth HS. Pituitary adenoma with neuronal choristoma (PANCH): composite lesion or lineage infidelity? Ultrastruct Pathol 1994;18:565–574.

    Google Scholar 

  14. Puchner MJA, Ludecke DK, Valdueza JM, Saeger W, Willig RP, Stalla GK, Odink RJ. Cushing' disease in a child caused by a corticotropin-releasing hormone-secreting intrasellar gangliocytoma associated with an adrenocorticotropic hormone-secreting pituitary adenoma. Neurosurgery 1993;33: 920–925.

    Google Scholar 

  15. Saeger W, Puchner MJA, Ludecke DK. Combined sellar gangliocytoma and pituitary adenoma in acromegaly or Cushing' disease. A report of 3 cases. Virchows Arch 1994;425: 93–99.

    Google Scholar 

  16. Pernicone PJ, Scheithauer BW, Sebo TJ, Kovacs KT, Horvath E, Young WF Jr, Lloyd RV, Davis DH, Guthrie BL, Schoene WC. Pituitary carcinoma. A clinicopathologic study of 15 cases. Cancer 1997;79:804–812.

    Google Scholar 

  17. Kovacs K, Lloyd RV, Horvath E. Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. Am J Pathol 1989;134:345–353.

    Google Scholar 

  18. Kovacs K, Stefaneanu L, Horvath E, Lloyd RV, Lancranjan I, Buchfelder M, Fahlbusch R. Effect of dopamine agonist medication on prolactin-producing pituitary adenomas. A morphologic study including immunocytochemistry, electron microscopy, and in situ hybridization. Virchows Arch Pathol Anat 1991;418:439–446.

    Google Scholar 

  19. Stefaneanu L, Kovacs K, Horvath E, Lloyd RV. In situ hybridization study of pro-opiomelanocortin (POMC) gene expression in human pituitary corticotrophs and their adenomas. Virchows Arch Pathol Anat 1991;419:107–113.

    Google Scholar 

  20. Stefaneanu L, Kovacs K, Horvath E, Lloyd RV, Buchfelder M, Fahlbusch R, Smyth H. In situ hybridization study of estrogen receptor messenger ribonucleic acid in human adenohypophysial cells and pituitary adenomas. J Clin Endocrinol Metab 1994;78:83–88.

    Google Scholar 

  21. Jin L, Qian X, Kulig E, Sanno N, Scheithauer BW, Kovacs K, Young WF Jr, Lloyd RV. Transforming growth factor-? receptor II and p27kip1 expression in nontumorous and neoplastic human pituitaries. Am J Pathol 1997;151:509–519.

    Google Scholar 

  22. Thorner MO, Perryman RL, Cronin MJ, et al. Somatotroph hyperplasia: Successful treatment of acromegaly by removal of pancreatic islet tumor secreting a growth hormone releasing factor. J Clin Invest 1982;70:965–977.

    Google Scholar 

  23. Sano T, Asa SL, Kovacs K. Growth hormone-releasing hormone-producing tumors: clinical, biochemical and morphological manifestations. Endocr Rev 1988;9:357–373.

    Google Scholar 

  24. Stefaneanu L, Kovacs K, Horvath E, Asa SL, Losinski NE, Billestrup N, Price J, Vale W. Adenohypophysial changes in mice transgenic for human growth hormone-releasing factor: A histologic, immunocytochemical, and electron microscopic investigation. Endocrinology 1989;125:2710–2718.

    Google Scholar 

  25. Asa SL, Kovacs K, Stefaneanu L, Horvath E, Billestrup N, Gonzales-Manchon C, Vale W. Pituitary adenomas in mice transgenic for growth hormone-releasing hormone. Endocrinology 1992;131:2083–2089.

    Google Scholar 

  26. Thapar K, Kovacs K, Stefaneanu L, Scheithauer BW, Killinger DW, Lloyd RV, Smyth HS, Barr A, Thorner MO, Gaylinn B, Laws ER Jr. Overexpression of the growth hormone-releasing hormone gene in acromegaly associated pituitary tumors: An event associated with neoplastic progression and aggressive behavior. Am J Pathol 1997;151:769–784.

    Google Scholar 

  27. Dubois PM, El Amraoui A, Heretier AG. Development and differentiation of pituitary cells. Microsc Res Tech 1997;39: 98–113.

    Google Scholar 

  28. Franke WW, Grund C, Archatatter T. Co-expression of cytokines and neurofilament proteins in a permanent cell line: Cultured rat PC12 cells combine neuronal and epithelial features. J Cell Biol 1986;103:1933–1943.

    Google Scholar 

  29. Tamir H, Liu KP, Payette RF. Human medullary thyroid carcinoma: Characterization of the serotoninergic and neuronal properties of a neuroectodermally derived cell line. J Neurosci 1989;9:1199–1212.

    Google Scholar 

  30. Altman H, Wigander AL, Nilsson O. Presence of nerve growth factor like immunoreactivity in carcinoid tumour cells and induction of a neuronal phenotype in long term culture. Int J Cancer 1989;43:949–955.

    Google Scholar 

  31. Polak M, Scharfmann R, Seilheimer B, Eisenbarth G, Dressler D, Verma IM, Porter H. Nerve growth factor induces neuron-like differentiation of an insulin-secreting pancreatic beta cell line. Proc Natl Acad Sci USA 1993;90: 5781–5785.

    Google Scholar 

  32. McCann FV, Pettengill OS, Cole JJ, Russell JAG, Sorenson GD. Calcium spike electrogenesis and other electrical activity in continuously cultured small cell carcinoma of the lung. Science 1981;212:1155–1157.

    Google Scholar 

  33. Martinez-Gampos A, Dannies PS. A possible differentiation of anterior pituitary cells in collagen gels into neurons. Cell Tissue Res 1986;244:21–26.

    Google Scholar 

  34. Schechter J, Windle JJ, Stauber C, Mellon PL. Neural tissue within anterior pituitary tumors generated by oncogene expression in transgenic mice. Neuroendocrinology 1992;56: 300–311.

    Google Scholar 

  35. Missale C, Boroni F, Sigala S, Zamellano A, Toso RD, Balsori A, Spano P. Nerve growth factor directs differentiation of the bipotential cell line GH-3 into the mammotroph phenotype. Endocrinology 1994;135:290–298.

    Google Scholar 

  36. Missale C, Boroni E, Fraasine M, Cariso A, Spano P. Nerve growth factor promotes the differentiation of pituitary mammotroph cells in vitro. Endocrinology 1995;136:1205-1213.

    Google Scholar 

  37. Missale C, Boroni F, Losa M, Giovanelli M, Zanellato A, Dal Toso R, Spano P. Nerve growth factor suppresses the transforming phenotype of human prolactinomas. Proc Natl Acad Sci USA 1993;90:7961–7965.

    Google Scholar 

  38. Borelli E, Sawchenko PE, Evans RM. Pituitary hyperplasia induced by ectopic expression of nerve growth factor. Proc Natl Acad Sci USA 1992;89:2764–2768.

    Google Scholar 

  39. Maness LM, Kastin AJ, Weber JT, Banks WA, Beckman BS, Zadine JE. The neurotrophins and their receptors: Structure, function, and neuropathology. Neurosci Behav Rev 1994;18:1:143–159.

    Google Scholar 

  40. Missale C, Boroni F, Sigala S, Burian A, Fabris M, Lean A, Dol Tosu R, Sparo PF. Nerve growth factor in the anterior pituitary: Localization in mammotroph cells and cosecretion with prolactin by a dopamine-regulated mechanism. Proc Natl Acad Sci USA 1996;93:4240–4245.

    Google Scholar 

  41. Missale C, Losa M, Sigala S, Balsani A, Giovanelli M, Spano PF. Nerve growth factor controls proliferation and progression of human prolactinoma cell lines through an autocrine mechanism. Mol Endocrinol 1996;10:272–285.

    Google Scholar 

  42. Melmed S, Ho K, Klibanski A, Reichlin S, Thorner M. Recent advances in pathogenesis, diagnosis, and management of acromegaly. J Clin Endocrinol Metab 1995;80:3395–3402.

    Google Scholar 

  43. Cittren L. The regulation of growth hormone secretion. Endocr Metab Clin N Am 1996;25:541–571.

    Google Scholar 

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Scheithauer, B., Horvath, E., Kovacs, K. et al. Prolactin-Producing Pituitary Adenoma and Carcinoma with Neuronal Components<197>A Metaplastic Lesion. Pituitary 1, 197–206 (1999). https://doi.org/10.1023/A:1009913303109

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