Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors

Archives of Pathology and Laboratory Medicine

Volumn 134, Issue 1, 2010, Pages 33-40

  Martignoni, Guido ^a   Pea, Maurizio ^a   Reghellin, Daniela ^b   Gobbo, Stefano ^a   Zamboni, Giuseppe ^a   Chilosi, Marco ^a   Bonetti, Franco ^a  

^a UNIVERSITY OF VERONA   (Italy)

^b ULSS 5 Ovest Vicentino   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN KINASE; TUBERIN; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; GENETICS; HUMAN; LYMPHANGIOLEIOMYOMATOSIS; PATHOLOGY; PERIVASCULAR EPITHELIOID CELL TUMOR; PHYSIOLOGY; SIGNAL TRANSDUCTION;

HUMANS; LYMPHANGIOLEIOMYOMATOSIS; PERIVASCULAR EPITHELIOID CELL NEOPLASMS; PROTEIN KINASES; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 75349104986     PISSN: 00039985     EISSN: 15432165     Source Type: Journal    
DOI: None     Document Type: Article

References (90)

1. European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993;75:1305-1315.
2. Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc. 2000;75:591-594.
3. Franz DN, Brody A, Meyer C, et al. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med. 2001;164:661-668.
4. Moss J, Avila NA, Barnes PM, et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med. 2001;164:669-671.
5. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277:805-808. (Pubitemid 27366729)
6. Steagall WK, Taveira-DaSilva AM, Moss J. Clinical and molecular insights into lymphangioleiomyomatosis. Sarcoidosis Vasc Diffuse Lung Dis. 2005; 22(suppl 1):S49-S66.
7. Travis WD, Colby TV, Koss MN, Rosado-de-Christenson ML, Muller NL, King TE. Non-neoplastic Disorders of the Lower Respiratory Tract. Washington, DC: American Registry of Pathology; 2002. Atlas of Nontumor Pathology; 1st series; fascicle 2.
8. Berger U, Khaghani A, Pomerance A, Yacoub MH, Coombes RC. Pulmonary lymphangioleiomyomatosis and steroid receptors: an immunocytochemical study. Am J Clin Pathol. 1990;93:609-614.
9. Bonetti F, Chiodera PL, Pea M, et al. Transbronchial biopsy in lymphangiomyomatosis of the lung: HMB45 for diagnosis. Am J Surg Pathol. 1993;17:1092-1102.
10. Bonetti F, Pea M, Martignoni G, Zamboni G, Iuzzolino P. Cellular heterogeneity in lymphangiomyomatosis of the lung. Hum Pathol. 1991;22:727-728.
11. Chan JK, Tsang WY, Pau MY, Tang MC, Pang SW, Fletcher CD. Lymphangiomyomatosis and angiomyolipoma: closely related entities characterized by hamartomatous proliferation of HMB-45-positive smooth muscle. Histopathology. 1993;22:445-455.
12. Graham ML II, Spelsberg TC, Dines DE, Payne WS, Bjornsson J, Lie JT. Pulmonary lymphangiomyomatosis: with particular reference to steroid-receptor assay studies and pathologic correlation. Mayo Clin Proc. 1984;59:3-11.
13. Kuhnen C, Preisler K, Muller KM. Pulmonary lymphangioleiomyomatosis: morphologic and immunohistochemical findings [in German]. Pathologe. 2001; 22:197-204.
14. Matsumoto Y, Horiba K, Usuki J, Chu SC, Ferrans VJ, Moss J. Markers of cell proliferation and expression of melanosomal antigen in lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 1999;21:327-336.
15. Ohori NP, Yousem SA, Sonmez-Alpan E, Colby TV. Estrogen and progesterone receptors in lymphangioleiomyomatosis, epithelioid hemangioendothelioma, and sclerosing hemangioma of the lung. Am J Clin Pathol. 1991;96: 529-535.
16. Zhe X, Schuger L. Combined smooth muscle and melanocytic differentiation in lymphangioleiomyomatosis. J Histochem Cytochem. 2004;52:1537-1542.
17. Bonetti F, Pea M, Martignoni G, et al. The perivascular epithelioid cell and related lesions. Adv Anat Pathol. 1997;4:343-358.
18. Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F. PEComas: the past, the present and the future. Virchows Arch. 2008;452:119-132.
19. Pea M, Martignoni G, Zamboni G, Bonetti F. Perivascular epithelioid cell. Am J Surg Pathol. 1996;20:1149-1153.
20. Folpe AL. Neoplasms with perivascular epithelioid cell differentiation (PEComas). In: Fletcher CD, Unni KK, Epstein J, Mertens F, eds. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, France: IARC; 2002:221-222. World Health Organization Classification of Tumours.
21. Bonetti F, Pea M, Martignoni G, et al. Clear cell ("sugar") tumor of the lung is a lesion strictly related to angiomyolipoma-the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC). Pathology. 1994;26:230-236.
22. Tazelaar HD, Batts KP, Srigley JR. Primary extrapulmonary sugar tumor (PEST): a report of four cases. Mod Pathol. 2001;14:615-622.
23. Folpe AL, Goodman ZD, Ishak KG, et al. Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults. Am J Surg Pathol. 2000;24:1239-1246.
24. Matsui K, Tatsuguchi A, Valencia J, et al. Extrapulmonary lymphangioleiomyomatosis (LAM): clinicopathologic features in 22 cases. Hum Pathol. 2000;31:1242-1248.
25. Jungbluth AA, Busam KJ, Gerald WL, et al. A103: an anti-melan-a monoclonal antibody for the detection of malignant melanoma in paraffinembedded tissues. Am J Surg Pathol. 1998;22:595-602.
26. Weeks DA, Malott RL, Arnesen M, Zuppan C, Aitken D, Mierau G. Hepatic angiomyolipoma with striated granules and positivity with melanoma-specific antibody (HMB-45): a report of two cases. Ultrastruct Pathol. 1991;15: 563-571.
27. Crisan M, Yap S, Casteilla L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3:301-313.
28. Eble JN. Angiomyolipoma of kidney. Semin Diagn Pathol. 1998;15:21-40.
29. Henske EP, Ao X, Short MP, et al. Frequent progesterone receptor immunoreactivity in tuberous sclerosis-associated renal angiomyolipomas. Mod Pathol. 1998;11:665-668.
30. L'Hostis H, Deminiere C, Ferriere JM, Coindre JM. Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow-up study of 46 cases. Am J Surg Pathol. 1999;23:1011-1020.
31. Stone CH, Lee MW, Amin MB, et al. Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum. Arch Pathol Lab Med. 2001;125:751-758.
32. Eble JN, Amin MB, Young RH. Epithelioid angiomyolipoma of the kidney: a report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol. 1997;21:1123-1130.
33. Martignoni G, Amin MB. Angiomyolipoma. In: Eble JN, Sauter G, Epstein J, Sesterhenn I, eds. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC Press; 2004:65-67. World Health Organization Classification of Tumours.
34. Pea M, Bonetti F, Zamboni G, Martignoni G, Fiore-Donati L, Doglioni C. Clear cell tumor and angiomyolipoma. Am J Surg Pathol. 1991;15:199-202.
35. Vang R, Kempson RL. Perivascular epithelioid cell tumor ('PEComa') of the uterus: a subset of HMB-45-positive epithelioid mesenchymal neoplasms with an uncertain relationship to pure smooth muscle tumors. Am J Surg Pathol. 2002;26: 1-13.
36. Pan CC, Yu IT, Yang AH, Chiang H. Clear cell myomelanocytic tumor of the urinary bladder. Am J Surg Pathol. 2003;27:689-692.
37. Pan CC, Yang AH, Chiang H. Malignant perivascular epithelioid cell tumor involving the prostate. Arch Pathol Lab Med. 2003;127(2):e96-e98.
38. Govender D, Sabaratnam RM, Essa AS. Clear cell 'sugar' tumor of the breast: another extrapulmonary site and review of the literature. Am J Surg Pathol. 2002;26:670-675.
39. Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F. Perivascular epithelioid cell tumor (PEComa) in the genitourinary tract. Adv Anat Pathol. 2007;14:36-41.
40. Nellist M, Van Slegtenhorst MA, Goedbloed M, Van Den Ouweland AM, Halley DJ, Van Der Sluijs P. Characterization of the cytosolic tuberin-hamartin complex: tuberin is a cytosolic chaperone for hamartin. J Biol Chem. 1999;274: 35647-35652.
41. Benvenuto G, Li S, Brown SJ, et al. The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination. Oncogene. 2000;19:6306-6316.
42. Kwiatkowski DJ. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet. 2003;67:87-96.
43. Carbonara C, Longa L, Grosso E, et al. Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas. Genes Chromosomes Cancer. 1996;15:18-25.
44. Pan CC, Jong YJ, Chai CY, Huang SH, Chen YJ. Comparative genomic hybridization study of perivascular epithelioid cell tumor: molecular genetic evidence of perivascular epithelioid cell tumor as a distinctive neoplasm. Hum Pathol. 2006;37:606-612.
45. Pan CC, Chung MY, Ng KF, et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol. 2008;214:387-393.
46. Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000;97:6085-6090. (Pubitemid 30367527)
47. Crooks DM, Pacheco-Rodriguez G, DeCastro RM, et al. Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2004;101:17462-17467.
48. Smolarek TA, Wessner LL, McCormack FX, Mylet JC, Menon AG, Henske EP. Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet. 1998;62: 810-815.
49. Strizheva GD, Carsillo T, Kruger WD, Sullivan EJ, Ryu JH, Henske EP. The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med. 2001;163:253-258.
50. Yu J, Astrinidis A, Henske EP. Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis. Am J Respir Crit Care Med. 2001;164:1537-1540.
51. Kenerson H, Folpe AL, Takayama TK, Yeung RS. Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol. 2007;38:1361-1371.
52. Martin KA, Blenis J. Coordinate regulation of translation by the PI 3-kinase and mTOR pathways. Adv Cancer Res. 2002;86:1-39.
53. Bissler JJ, McCormack FX, Young LR, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008;358:140-151.
54. Davies DM, Johnson SR, Tattersfield AE, et al. Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med. 2008; 358:200-203.
55. Taille C, Debray MP, Crestani B. Sirolimus treatment for pulmonary lymphangioleiomyomatosis. Ann Intern Med. 2007;146:687-688.
56. Mansky KC, Marfatia K, Purdom GH, Luchin A, Hume DA, Ostrowski MC. The microphthalmia transcription factor (MITF) contains two N-terminal domains required for transactivation of osteoclast target promoters and rescue of mi mutant osteoclasts. J Leukoc Biol. 2002;71:295-303.
57. Mansky KC, Sulzbacher S, Purdom G, et al. The microphthalmia transcription factor and the related helix-loop-helix zipper factors TFE-3 and TFE-C collaborate to activate the tartrate-resistant acid phosphatase promoter. J Leukoc Biol. 2002;71:304-310.
58. Steingrimsson E, Tessarollo L, Pathak B, et al. Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development. Proc Natl Acad Sci U S A. 2002;99:4477-4482.
59. Shahlaee AH, Brandal S, Lee YN, Jie C, Takemoto CM. Distinct and shared transcriptomes are regulated by microphthalmia-associated transcription factor isoforms in mast cells. J Immunol. 2007;178:378-388.
60. Drake FH, Dodds RA, James IE, et al. Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J Biol Chem. 1996;271: 12511-12516.
61. Hershey CL, Fisher DE. Genomic analysis of the Microphthalmia locus and identification of the MITF-J/Mitf-J isoform. Gene. 2005;347:73-82.
62. Inaoka T, Bilbe G, Ishibashi O, Tezuka K, Kumegawa M, Kokubo T. Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone. Biochem Biophys Res Commun. 1995;206: 89-96.
63. Meadows NA, Sharma SM, Faulkner GJ, Ostrowski MC, Hume DA, Cassady AI. The expression of Clcn7 and Ostm1 in osteoclasts is coregulated by microphthalmia transcription factor. J Biol Chem. 2007;282:1891-1904.
64. Motyckova G, Weilbaecher KN, Horstmann M, Rieman DJ, Fisher DZ, Fisher DE. Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression by the microphthalmia transcription factor family. Proc Natl Acad Sci U S A. 2001;98:5798-5803.
65. Takeda K, Yasumoto K, Kawaguchi N, et al. Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations. Biochim Biophys Acta. 2002;1574:15-23.
66. Glantschnig H, Fisher JE, Wesolowski G, Rodan GA, Reszka AA. M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ. 2003;10:1165-1177.
67. Quintanilla-Dieck MJ, Codriansky K, Keady M, Bhawan J, Runger TM. Cathepsin K in melanoma invasion. J Invest Dermatol. 2008;128:2281-2288.
68. Arch Pathol Lab Med-Vol 134, January 2010 Lymphangioleiomyomatosis and PEComas-Martignoni et al 39
69. Karbowniczek M, Spittle CS, Morrison T, Wu H, Henske EP. mTOR is activated in the majority of malignant melanomas. J Invest Dermatol. 2008;128: 980-987.
70. Kneissel M, Luong-Nguyen NH, Baptist M, et al. Everolimus suppresses cancellous bone loss, bone resorption, and cathepsin K expression by osteoclasts. Bone. 2004;35:1144-1156.
71. Chilosi M, Pea M, Martignoni G, et al. Cathepsin-k expression in pulmonary lymphangioleiomyomatosis. Mod Pathol. 2009;22:161-166.
72. Goncharova EA, Goncharov DA, Eszterhas A, et al. Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation: a role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem. 2002;277:30958-30967.
73. Karbowniczek M, Astrinidis A, Balsara BR, et al. Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. Am J Respir Crit Care Med. 2003;167:976-982.
74. Lesma E, Grande V, Ancona S, Carelli S, Di Giulio AM, Gorio A. Anti- EGFR antibody efficiently and specifically inhibits human TSC2-/- smooth muscle cell proliferation. Possible treatment options for TSC and LAM. PLoS One. 2008; 3:e3558.
75. Kawaguchi K, Oda Y, Nakanishi K, et al. Malignant transformation of renal angiomyolipoma: a case report. Am J Surg Pathol. 2002;26:523-529.
76. Martignoni G, Pea M, Bonetti F, et al. Carcinomalike monotypic epithelioid angiomyolipoma in patients without evidence of tuberous sclerosis: a clinicopathologic and genetic study. Am J Surg Pathol. 1998;22:663-672.
77. Martignoni G, Pea M, Rigaud G, et al. Renal angiomyolipoma with epithelioid sarcomatous transformation and metastases: demonstration of the same genetic defects in the primary and metastatic lesions. Am J Surg Pathol. 2000;24:889-894.
78. Ma L, Kowalski D, Javed K, Hui P. Atypical angiomyolipoma of kidney in a patient with tuberous sclerosis: a case report with p53 gene mutation analysis. Arch Pathol Lab Med. 2005;129:676-679.
79. Brentani MM, Carvalho CR, Saldiva PH, Pacheco MM, Oshima CT. Steroid receptors in pulmonary lymphangiomyomatosis. Chest. 1984;85:96-99.
80. Matsui K, Takeda K, Yu ZX, et al. Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy: an immunohistochemical study. Am J Respir Crit Care Med. 2000;161:1002-1009.
81. Svendsen TL, Viskum K, Hansborg N, Thorpe SM, Nielsen NC. Pulmonary lymphangioleiomyomatosis: a case of progesterone receptor positive lymphangioleiomyomatosis treated with medroxyprogesterone, oophorectomy and tamoxifen. Br J Dis Chest. 1984;78:264-271.
82. Urban T, Lazor R, Lacronique J, et al. Pulmonary lymphangioleiomyomatosis: a study of 69 patients-Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P). Medicine (Baltimore). 1999;78:321-337.
83. Harari S, Cassandro R, Chiodini J, Taveira-DaSilva AM, Moss J. Effect of a gonadotrophin-releasing hormone analogue on lung function in lymphangioleiomyomatosis. Chest. 2008;133:448-454.
84. Schiavina M, Contini P, Fabiani A, et al. Efficacy of hormonal manipulation in lymphangioleiomyomatosis: a 20-year-experience in 36 patients. Sarcoidosis Vasc Diffuse Lung Dis. 2007;24:39-50.
85. Taveira-DaSilva AM, Stylianou MP, Hedin CJ, Hathaway O, Moss J. Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone. Chest. 2004;126:1867-1874.
86. Glassberg MK, Elliot SJ, Fritz J, et al. Activation of the estrogen receptor contributes to the progression of pulmonary lymphangioleiomyomatosis via matrix metalloproteinase-induced cell invasiveness. J Clin Endocrinol Metab. 2008;93:1625-1633.
87. Yu JJ, Robb VA, Morrison TA, et al. Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells. Proc Natl Acad Sci U S A. 2009;106: 2635-2640.
88. Pacheco-Rodriguez G, Steagall WK, Crooks DM, et al. TSC2 loss in lymphangioleiomyomatosis cells correlated with expression of CD44v6, a molecular determinant of metastasis. Cancer Res. 2007;67:10573-10581.
89. Henske EP. Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosomes Cancer. 2003;38:376-381.
90. Glasgow CG, Taveira-Dasilva AM, Darling TN, Moss J. Lymphatic involvement in lymphangioleiomyomatosis. Ann N Y Acad Sci. 2008;1131: 206-214.