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Published in:

01-01-2006 | Review

The 2004 World Health Organization classification of pituitary tumors: What is new?

Authors: Mubarak Al-Shraim, Sylvia L Asa

Published in: Acta Neuropathologica | Issue 1/2006

Abstract

The classification of pituitary tumors is a dynamic area that changes with advances in cell biology that provide a deeper insight and clearer understanding of cell lineages and pathogenetic mechanisms. The 2004 edition of the World Heath Organization (WHO) text “Histological typing of endocrine tumors” reflects the progress that has been achieved since the previous edition of 2000. Here we review the new information and identify areas of concern for the next effort at classification of pituitary tumors.

Abbass SAA, Asa SL, Ezzat S (1997) Altered expression of fibroblast growth factor receptors in human pituitary adenomas. J Clin Endocrinol Metab 82:1160–1166CrossRefPubMed

Amar AP, Hinton DR, Krieger MD, Weiss MH (1999) Invasive pituitary adenomas: significance of proliferation parameters. Pituitary 2:117–212CrossRefPubMed

Asa SL (1998) Tumors of the pituitary gland. Atlas of tumor pathology, Third Series, Fascicle 22. Armed Forces Institute of Pathology, Washington D.C.

Asa SL, Ezzat S (1998) The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 19:798–827CrossRefPubMed

Asa SL, Ezzat S (1999) Molecular determinants of pituitary cytodifferentiation. Pituitary 1:159–168CrossRefPubMed

Asa SL, Ezzat S (2002) The pathogenesis of pituitary tumours. Nat Rev Cancer 2:836–849CrossRefPubMed

Asa SL, Ezzat S (2004) Molecular basis of pituitary development and cytogenesis. Front Horm Res 32:1–19PubMed

Asa SL, Gerrie BM, Singer W, Horvath E, Kovacs K, Smyth HS (1986) Gonadotropin secretion in vitro by human pituitary null cell adenomas and oncocytomas. J Clin Endocrinol Metab 62:1011–1019PubMed

Asa SL, Cheng Z, Ramyar L, Singer W, Kovacs K, Smyth HS, Muller P (1992) Human pituitary null cell adenomas and oncocytomas in vitro: effects of adenohypophysiotropic hormones and gonadal steroids on hormone secretion and tumor cell morphology. J Clin Endocrinol Metab 74:1128–1134CrossRefPubMed

10.

Asa SL, Bamberger A-M, Cao B, Wong M, Parker KL, Ezzat S (1996) The transcription activator steroidogenic factor-1 is preferentially expressed in the human pituitary gonadotroph. J Clin Endocrinol Metab 81:2165–2170CrossRefPubMed

11.

Asa SL, Somers K, Ezzat S (1998) The MEN-1 gene is rarely down-regulated in pituitary adenomas. J Clin Endocrinol Metab 83:3210–3212CrossRefPubMed

12.

Asa SL, Ramyar L, Murphy PR, Li AW, Ezzat S (2001) The endogenous fibroblast growth factor-2 antisense gene product regulates pituitary cell growth and hormone production. Mol Endocrinol 15:589–599CrossRefPubMed

13.

Bahar A, Bicknell JE, Simpson DJ, Clayton RN, Farrell WE (2004) Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation. Oncogene 23:936–944CrossRefPubMed

14.

Bamberger CM, Fehn M, Bamberger AM, Ludecke DK, Beil FU, Saeger W, Schulte HM (1999) Reduced expression levels of the cell-cycle inhibitor p27Kip1 in human pituitary adenomas. Eur J Endocrinol 140:250–255CrossRefPubMed

15.

Bhayana S., Booth G, Kovacs K, Asa SL, Ezzat S (2005) J Clin Endocrinol Metab (in press)

16.

Boelaert K, McCabe CJ, Tannahill LA, Gittoes NJ, Holder RL, Watkinson JC, Bradwell AR, Sheppard MC, Franklyn JA (2003) Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer. J Clin Endocrinol Metab 88:2341–2347CrossRefPubMed

17.

Buckley N, Bates AS, Broome JC, Strange RC, Perrett CW, Burke CW, Clayton RN (1994) p53 protein accumulation in Cushings adenomas and invasive non-functional adenomas. J Clin Endocrinol Metab 79:1513–1516CrossRefPubMed

18.

Dahia PL, Aguiar RC, Honegger J, Fahlbush R, Jordan S, Lowe DG, Lu X, Clayton RN, Besser GM, Grossman AB (1998) Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours. Oncogene 16:69–76CrossRefPubMed

19.

DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) (2004) World Health Organization classification of tumours: Tumours of endocrine organs. IARC, Lyons

20.

Ezzat S, Horvath E, Kovacs K, Smyth HS, Singer W, Asa SL (1995) Basic fibroblast growth factor expression by two prolactin and thyrotropin-producing pituitary adenomas. Endocr Pathol 6:125–134PubMed

21.

Ezzat S, Kontogeorgos G, Redelmeier DA, Horvath E, Harris AG, Kovacs K (1995) In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide. Eur J Endocrinol 133:686–690PubMed

22.

Ezzat S, Smyth HS, Ramyar L, Asa SL (1995) Heterogeneous in vivo and in vitro expression of basic fibroblast growth factor by human pituitary adenomas. J Clin Endocrinol Metab 80:878–884CrossRefPubMed

23.

Ezzat S, Walpola IA, Ramyar L, Smyth HS, Asa SL (1995) Membrane-anchored expression of transforming growth factor-α in human pituitary adenoma cells. J Clin Endocrinol Metab 80:534–539CrossRefPubMed

24.

Ezzat S, Zheng L, Zhu XF, Wu GE, Asa SL (2002) Targeted expression of a human pituitary tumor-derived isoform of FGF receptor-4 recapitulates pituitary tumorigenesis. J Clin Invest 109:69–78CrossRefPubMed

25.

Ezzat S, Yu S, Asa SL (2003) Ikaros isoforms in human pituitary tumors: distinct localization, histone acetylation, and activation of the 5’ fibroblast growth factor receptor-4 promoter. Am J Pathol 163:1177–1184PubMed

26.

Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE (2004) The prevalence of pituitary adenomas: a systematic review. Cancer 101:613–619CrossRefPubMed

27.

Ezzat S, Zheng L, Asa SL (2004) Pituitary tumor-derived fibroblast growth factor receptor 4 isoform disrupts neural cell-adhesion molecule/N-cadherin signaling to diminish cell adhesiveness: a mechanism underlying pituitary neoplasia. Mol Endocrinol 18:2543–2552CrossRefPubMed

28.

Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, Polyak K, Tsai LH, Broudy V, Perlmutter RM, Kauschansky K, Roberts JM (1996) A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27^Kip1-deficient mice. Cell 85:733–744CrossRefPubMed

29.

Franklin DS, Godfrey VL, Lee H, Kovalev GI, Schoonhoven R, Chen-Kiang S, Su L, Xiong Y (1998) CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis. Genes Dev 12:2899–2911PubMed

30.

Hibberts NA, Simpson DJ, Bicknell JE, Broome JC, Hoban PR, Clayton RN, Farrell WE (1999) Analysis of cyclin D1 (CCND1) allelic imbalance and overexpression in sporadic human pituitary tumors. Clin Cancer Res 5:2133–2139PubMed

31.

Horvath E, Kovacs K (1984) Gonadotroph adenomas of the human pituitary: sex-related fine-structural dichotomy. A histologic, immunocytochemical, and electron-microscopic study of 30 tumors. Am J Pathol 117:429–440PubMed

32.

Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W (1980) Silent corticotropic adenomas of the human pituitary gland. A histologic, immunocytologic, and ultrastructural study. Am J Pathol 98:617–638PubMed

33.

Horvath E, Kovacs K, Smyth HS, Killinger DW, Scheithauer BW, Randall R, Laws ER Jr, Singer W (1988) A novel type of pituitary adenoma: Morphological feature and clinical correlations. J Clin Endocrinol Metab 66:1111–1118PubMed

34.

Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA (1992) Effects of an Rb mutation in the mouse. Nature 359:295–300CrossRefPubMed

35.

Jin L, Qian X, Kulig E, Sanno N, Scheithauer BW, Kovacs K, Young WF Jr, Lloyd RV (1997) Transforming growth factor-beta, transforming growth factor-beta receptor II, and p27Kip1 expression in nontumorous and neoplastic human pituitaries. Am J Pathol 151:509–519PubMed

36.

Jordan S, Lidhar K, Korbonits M, Lowe DG, Grossman AB (2000) Cyclin D and cyclin E expression in normal and adenomatous pituitary. Eur J Endocrinol 143:R1–R6CrossRefPubMed

37.

Kiyokawa H, Kineman RD, Manova-Todorova KO, Soares VC, Hoffman ES, Ono M, Khanam D, Hayday AC, Frohman LA, Koff A (1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27^Kip1. Cell 85:721–732CrossRefPubMed

38.

Knosp E, Kitz K, Perneczky A (1989) Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. Neurosurgery 25:927–930CrossRefPubMed

39.

Kovacs K, Horvath E, Bayley TA, Hassaram ST, Ezrin C (1978) Silent corticotroph cell adenoma with lysosomal accumulation and crinophagy. A distinct clinicopathologic entity. Am J Med 64:492–499CrossRefPubMed

40.

Kovacs K, Horvath E, Ryan N, Ezrin C (1980) Null cell adenoma of the human pituitary. Virchows Arch [A] 387:165–174

41.

Labat-Moleur F, Trouillas J, Seret-Begue D, Kujas M, Delisle M-B, Ronin C (1991) Evaluation of 29 monoclonal and polyclonal antibodies used in the diagnosis of pituitary adenomas. A collaborative study from pathologists of the Club Français de l’Hypophyse. Pathol Res Pract 187:534–538PubMed

42.

Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L (1989) GTPase inhibiting mutations activate the alpha-chain of Gs and stimulate adenylate cyclase in human pituitary tumors. Nature 340:692–696CrossRefPubMed

43.

LeRiche V, Asa SL, Ezzat S (1996) Epidermal growth factor and its receptor (EGF-R) in human pituitary adenomas: EGF-R correlates with tumor aggressiveness. J Clin Endocrinol Metab 81:656–662CrossRefPubMed

44.

Lidhar K, Korbonits M, Jordan S, Khalimova Z, Kaltsas G, Lu X, Clayton RN, Jenkins PJ, Monson JP, Besser GM, Lowe DG, Grossman AB (1999) Low expression of the cell cycle inhibitor p27Kip1 in normal corticotroph cells, corticotroph tumors, and malignant pituitary tumors. J Clin Endocrinol Metab 84:3823–3830CrossRefPubMed

45.

McAndrew J, Paterson AJ, Asa SL, McCarthy KJ, Kudlow JE (1995) Targeting of transforming growth factor-α expression to pituitary lactotrophs in transgenic mice results in selective lactotroph proliferation and adenomas. Endocrinology 136:4479–4488CrossRefPubMed

46.

Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, Shisido N, Horii I, Loh DY (1996) Mice lacking p27^Kip1 display increased body size,multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85:707–720CrossRefPubMed

47.

Pei L, Melmed S (1997) Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol 11:433–441CrossRefPubMed

48.

Pei L, Melmed S, Scheithauer B, Kovacs K, Prager D (1994) H-ras mutations in human pituitary carcinoma metastases. J Clin Endocrinol Metab 78:842–846CrossRefPubMed

49.

Qian ZR, Sano T, Asa SL, Yamada S, Horiguchi H, Tashiro T, Li CC, Hirokawa M, Kovacs K, Ezzat S (2004) Cytoplasmic expression of fibroblast growth factor receptor-4 in human pituitary adenomas: relation to tumor type, size, proliferation, and invasiveness. J Clin Endocrinol Metab 89:1904–1911CrossRefPubMed

50.

Riss D, Jin L, Qian X, Bayliss J, Scheithauer BW, Young WF Jr, Vidal S, Kovacs K, Raz A, Lloyd RV (2003) Differential expression of galectin-3 in pituitary tumors. Cancer Res 63:2251–2255PubMed

51.

Sano T, Kovacs K, Asa SL, Yamada S, Sanno N, Yokoyama S, Takami H (2002) Pituitary adenoma with “honeycomb Golgi” appearance showing a phenotypic change at recurrence from clinically nonfunctioning to typical Cushing disease. Endocr Pathol 13:125–130CrossRefPubMed

52.

Sano T, Mader R, Asa SL, Qian ZR, Hino A, Yamada S (2003) “Honeycomb Golgi” in pituitary adenomas: not a marker of gonadotroph adenomas. Endocr Pathol 14:363–368CrossRefPubMed

53.

Shimon I, Hüttner A, Said J, Spirna OM, Melmed S (1996) Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription. J Clin Invest 97:187–195PubMed

54.

Shimon I, Hinton DR, Weiss MH, Melmed S (1998) Prolactinomas express human heparin-binding secretory transforming gene (hst) protein product: marker of tumour invasiveness. Clin Endocrinol (Oxf) 48:23–29

55.

Simpson DJ, Bicknell JE, McNicol AM, Clayton RN, Farrell WE (1999) Hypermethylation of the p16/CDKN2A/MTSI gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas. Genes Chromosomes Cancer 24:328–336CrossRefPubMed

56.

Simpson DJ, Hibberts NA, McNicol AM, Clayton RN, Farrell WE (2000) Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island. Cancer Res 60:1211–1216PubMed

57.

Spada A, Vallar L, Faglia G (1992) G protein oncogenes in pituitary tumors. Trends Endocrinol Metab 3:355–360CrossRef

58.

Thakker RV, Pook MA, Wooding C, Boscaro M, Scanarini M, Clayton RN (1993) Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations. J Clin Invest 91:2815–2821PubMed

59.

Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER Jr (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–107CrossRefPubMed

60.

Thapar K, Scheithauer BW, Kovacs K, Pernicone PJ, Laws ER Jr (1996) p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 38:765–771CrossRefPubMed

61.

Vidal S, Kovacs K, Horvath E, Rotondo F, Kuroki T, Lloyd RV, Scheithauer BW (2002) Topoisomerase II alpha expression in pituitary adenomas and carcinomas: relationship to tumor behavior. Mod Pathol 15:1205–1212CrossRefPubMed

62.

Vidal S, Kovacs K, Bell D, Horvath E, Scheithauer BW, Lloyd RV (2003) Cyclooxygenase-2 expression in human pituitary tumors. Cancer 97:2814–2821CrossRefPubMed

63.

Yamada S, Asa SL, Kovacs K (1988) Oncocytomas and null cell adenomas of the human pituitary: morphometric and in vitro functional comparison. Virchows Arch [A] 413:333–339

64.

Yoshino A, Katayama Y, Fukushima T, Watanabe T, Komine C, Yokoyama T, Kusama K, Moro I (2003) Telomerase activity in pituitary adenomas: significance of telomerase expression in predicting pituitary adenoma recurrence. J Neurooncol 63:155–162CrossRefPubMed

65.

Zhang X, Sun H, Danila DC, Johnson SR, Zhou Y, Swearingen B, Klibanski A (2002) Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas: implications for tumorigenesis. J Clin Endocrinol Metab 87:1262–1267CrossRefPubMed

66.

Zhu J, Leon SP, Beggs AH, Busque L, Gilliland DG, Black PM (1994) Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus. J Clin Endocrinol Metab 78:922–927CrossRefPubMed

67.

Zhuang Z, Ezzat S, Vortmeyer AO, Weil R, Oldfield EH, Park W-S, Pack S, Huang S, Agarwal SK, Guru SC, et al (1997) Mutations of the MEN1 tumor suppressor gene in pituitary tumors. Cancer Res 57:5446–5451PubMed

68.

Zou H, McGarry TJ, Bernal T, Kirschner MW (1999) Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285:418–422CrossRefPubMed

Title: The 2004 World Health Organization classification of pituitary tumors: What is new?
Authors: Mubarak Al-Shraim
Sylvia L Asa
Publication date: 01-01-2006
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 1/2006
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-005-1093-6

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Springer Medicine

The 2004 World Health Organization classification of pituitary tumors: What is new?

Abstract

At a glance: The STEP trials

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Abstract

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