Best Practice & Research Clinical Obstetrics & Gynaecology
Volume 25, Issue 6 , Pages 691-704 , December 2011

Pathology of uterine leiomyosarcomas and smooth muscle tumours of uncertain malignant potential

  • Philip P.C. Ip, MBChB FRCPath (Clinical Associate Professor)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +852 2255 4732; Fax: +852 2872 8098.
  • ,
  • Annie N.Y. Cheung, MD FRCPath (Professor)

References 

  1. Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer. 1993 Feb 15;71(4 Suppl.):1702–1709
  2. Leibsohn S, d’Ablaing G, Mishell DR, et al. Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. Am J Obstet Gynecol. 1990;162:968–974discussion 74–76
  3. Danielson LS, Menendez S, Attolini CS, et al. A differentiation-based microRNA signature identifies leiomyosarcoma as a mesenchymal stem cell-related malignancy. Am J Pathol. 2010;177:908–917
  4. Mittal KR, Chen F, Wei JJ, et al. Molecular and immunohistochemical evidence for the origin of uterine leiomyosarcomas from associated leiomyoma and symplastic leiomyoma-like areas. Mod Pathol. 2009 Oct;22:1303–1311
  5. Yanai H, Wani Y, Notohara K, et al. Uterine leiomyosarcoma arising in leiomyoma: clinicopathological study of four cases and literature review. Pathol Int. 2010;60:506–509
  6. Zhang P, Zhang C, Hao J, et al. Use of X-chromosome inactivation pattern to determine the clonal origins of uterine leiomyoma and leiomyosarcoma. Hum Pathol. 2006;37:1350–1356
  7. Mittal K, Popiolek D, Demopoulos RI. Uterine myxoid leiomyosarcoma within a leiomyoma. Hum Pathol. 2000;31:398–400
  8. Mittal K, Joutovsky A. Areas with benign morphologic and immunohistochemical features are associated with some uterine leiomyosarcomas. Gynecol Oncol. 2007;104:362–365
  9. Clement PB, Young RH. Mesenchymal and mixed epithelial-mesenchymal tumors of the uterine corpus and cervix. In: Atlas of gynecologic surgical pathology. 2nd ed.. Philadelphia: WB Saunders; 2007;p. 194–235
  10. Clement PB. The pathology of uterine smooth muscle tumors and mixed endometrial stromal-smooth muscle tumors: a selective review with emphasis on recent advances. Int J Gynecol Pathol. 2000;19:39–55
  11. Hendrickson MR, Tavassoli FA, Kempson RL, et al. Mesenchymal tumours and related lesions. In:  Tavassoli FA,  Devilee P editor. World Health Organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press; 2003;p. 236–243
  12. Bell SW, Kempson RL, Hendrickson MR. Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol. 1994;18:535–558
  13. Ip PP, Tse KY, Tam KF. Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: a review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy. Adv Anat Pathol. 2010;17:91–112
  14. Ip PP, Lam KW, Cheung CL, et al. Tranexamic acid-associated necrosis and intralesional thrombosis of uterine leiomyomas: a clinicopathologic study of 147 cases emphasizing the importance of drug-induced necrosis and early infarcts in leiomyomas. Am J Surg Pathol. 2007;31:1215–1224
  15. Gao HG, LiVolsi VA, Zhang PJ. Utility of trichrome and reticulin stains in characterizing necroses in uterine smooth muscle tumors [abstract]. Mod Pathol. 2007;20:198A
  16. Ip PP, Cheung AN, Clement PB. Uterine smooth muscle tumors of uncertain malignant potential (STUMP): a clinicopathologic analysis of 16 cases. Am J Surg Pathol. 2009;33:992–1005
  17. Oliva E, Young RH, Amin MB, et al. An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies. Am J Surg Pathol. 2002;26:403–412
  18. Rizeq MN, van de Rijn M, Hendrickson MR, et al. A comparative immunohistochemical study of uterine smooth muscle neoplasms with emphasis on the epithelioid variant. Hum Pathol. 1994;25:671–677
  19. de Leval L, Waltregny D, Boniver J, et al. Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus. Am J Surg Pathol. 2006;30:319–327
  20. Liang J, Wu L, Xiao H, et al. Use of myocardin in the classification of mesenchymal tumors of the uterus. Int J Gynecol Pathol. 2010;29:55–62
  21. Prayson RA, Goldblum JR, Hart WR. Epithelioid smooth-muscle tumors of the uterus: a clinicopathologic study of 18 patients. Am J Surg Pathol. 1997;21:383–391
  22. Kurman RJ, Norris HJ. Mesenchymal tumors of the uterus. VI. Epithelioid smooth muscle tumors including leiomyoblastoma and clear-cell leiomyoma: a clinical and pathologic analysis of 26 cases. Cancer. 1976;37:1853–1865
  23. Oliva E, Nielson GP, Clement PB, et al. Epithelioid smooth muscle tumors of the uterus. A clinicopathologic analysis of 80 cases [abstract]. Mod Pathol. 1997;10:107A
  24. Atkins K, Bell SW, Kempson RL, et al. Epithelioid smooth muscle tumors of the uterus [abstract]. Mod Pathol. 2001;14:132A
  25. Silva EG, Deavers MT, Bodurka DC, et al. Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and the concept of PEComa. Am J Surg Pathol. 2004;28:244–249
  26. Folpe AL, Mentzel T, Lehr HA, et al. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol. 2005;29:1558–1575
  27. 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
  28. Hornick JL, Fletcher CD. Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. Am J Surg Pathol. 2008;32:493–501
  29. Atkins K, Bell SW, Kempson RL. Myxoid smooth muscle tumors of the uterus [abstract]. Mod Pathol. 2001;14:132A
  30. Lee FY, Wen MC, Wang J. Epithelioid leiomyosarcoma of the uterus containing sex cord-like elements. Int J Gynecol Pathol. 2010;29:67–68
  31. Grayson W, Fourie J, Tiltman AJ. Xanthomatous leiomyosarcoma of the uterine cervix. Int J Gynecol Pathol. 1998;17:89–90
  32. Shintaku M, Sekiyama K. Leiomyosarcoma of the uterus with focal rhabdomyosarcomatous differentiation. Int J Gynecol Pathol. 2004;23:188–192
  33. Darby AJ, Papadaki L, Beilby JO. An unusual leiomyosarcoma of the uterus containing osteoclast-like giant cells. Cancer. 1975;36:495–504
  34. Jones MW, Norris HJ. Clinicopathologic study of 28 uterine leiomyosarcomas with metastasis. Int J Gynecol Pathol. 1995;14:243–249
  35. McDonald AG, Dal Cin P, Ganguly A, et al. Liposarcoma arising in uterine lipoleiomyoma: a report of 3 cases and review of the literature. Am J Surg Pathol. 2011;35:221–227
  36. Vakiani M, Mawad J, Talerman A. Heterologous sarcomas of the uterus. Int J Gynecol Pathol. 1982;1:211–219
  37. Bapat K, Brustein S. Uterine sarcoma with liposarcomatous differentiation: report of a case and review of the literature. Int J Gynaecol Obstet. 1989;28:71–75
  38. Atkins KA, Arronte N, Darus CJ, et al. The use of p16 in enhancing the histologic classification of uterine smooth muscle tumors. Am J Surg Pathol. 2008;32:98–102
  39. Bodner-Adler B, Bodner K, Czerwenka K, et al. Expression of p16 protein in patients with uterine smooth muscle tumors: an immunohistochemical analysis. Gynecol Oncol. 2005;96:62–66
  40. O’Neill CJ, McBride HA, Connolly LE, et al. Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of uncertain malignant potential. Histopathology. 2007;50:851–858
  41. Blom R, Guerrieri C, Stal O, et al. Leiomyosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases. Gynecol Oncol. 1998;68:54–61
  42. de Vos S, Wilczynski SP, Fleischhacker M, et al. p53 alterations in uterine leiomyosarcomas versus leiomyomas. Gynecol Oncol. 1994;54:205–208
  43. Hall KL, Teneriello MG, Taylor RR, et al. Analysis of Ki-ras, p53, and MDM2 genes in uterine leiomyomas and leiomyosarcomas. Gynecol Oncol. 1997;65:330–335
  44. Jeffers MD, Farquharson MA, Richmond JA, et al. p53 immunoreactivity and mutation of the p53 gene in smooth muscle tumours of the uterine corpus. J Pathol. 1995;177:65–70
  45. Niemann TH, Raab SS, Lenel JC, et al. p53 protein overexpression in smooth muscle tumors of the uterus. Hum Pathol. 1995;26:375–379
  46. Sprogoe-Jakobsen S, Holund B. Immunohistochemistry (Ki-67 and p53) as a tool in determining malignancy in smooth muscle neoplasms (exemplified by a myxoid leiomyosarcoma of the uterus). APMIS. 1996;104:705–708
  47. Mayerhofer K, Lozanov P, Bodner K, et al. Ki-67 expression in patients with uterine leiomyomas, uterine smooth muscle tumors of uncertain malignant potential (STUMP) and uterine leiomyosarcomas (LMS). Acta Obstet Gynecol Scand. 2004;83:1085–1088
  48. Mittal K, Demopoulos RI. MIB-1 (Ki-67), p53, estrogen receptor, and progesterone receptor expression in uterine smooth muscle tumors. Hum Pathol. 2001;32:984–987
  49. Zhai YL, Kobayashi Y, Mori A, et al. Expression of steroid receptors, Ki-67, and p53 in uterine leiomyosarcomas. Int J Gynecol Pathol. 1999;18:20–28
  50. Leitao MM, Soslow RA, Nonaka D, et al. Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma. Cancer. 2004;101:1455–1462
  51. Lasota J, Jasinski M, Sarlomo-Rikala M, et al. Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol. 1999;154:53–60
  52. Rushing RS, Shajahan S, Chendil D, et al. Uterine sarcomas express KIT protein but lack mutation(s) in exon 11 or 17 of c-KIT. Gynecol Oncol. 2003;91:9–14
  53. Serrano C, Mackintosh C, Herrero D, et al. Imatinib is not a potential alternative treatment for uterine leiomyosarcoma. Clin Cancer Res. 2005;11:4977–4979author reply 9–80
  54. Ahvenainen T, Lehtonen HJ, Lehtonen R, et al. Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer. Cancer Genet Cytogenet. 2008;183:83–88
  55. Tomlinson IP, Alam NA, Rowan AJ, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet. 2002;30:406–410
  56. Ylisaukko-oja SK, Kiuru M, Lehtonen HJ, et al. Analysis of fumarate hydratase mutations in a population-based series of early onset uterine leiomyosarcoma patients. Int J Cancer. 2006;119:283–287
  57. Sandberg AA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: leiomyosarcoma. Cancer Genet Cytogenet. 2005;161:1–19
  58. Cho YL, Bae S, Koo MS, et al. Array comparative genomic hybridization analysis of uterine leiomyosarcoma. Gynecol Oncol. 2005;99:545–551
  59. Levy B, Mukherjee T, Hirschhorn K. Molecular cytogenetic analysis of uterine leiomyoma and leiomyosarcoma by comparative genomic hybridization. Cancer Genet Cytogenet. 2000;121:1–8
  60. Quade BJ, Wang TY, Sornberger K, et al. Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling. Genes Chromosomes Cancer. 2004;40:97–108
  61. Matsumura N, Mandai M, Miyanishi M, et al. Oncogenic property of acrogranin in human uterine leiomyosarcoma: direct evidence of genetic contribution in in vivo tumorigenesis. Clin Cancer Res. 2006;12:1402–1411
  62. Skubitz KM, Skubitz AP. Differential gene expression in leiomyosarcoma. Cancer. 2003;98:1029–1038
  63. Skubitz KM, Skubitz AP. Differential gene expression in uterine leiomyoma. J Lab Clin Med. 2003;141:297–308
  64. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–838
  65. Pan Q, Luo X, Chegini N. microRNA 21: response to hormonal therapies and regulatory function in leiomyoma, transformed leiomyoma and leiomyosarcoma cells. Mol Hum Reprod. 2010;16:215–227
  66. Pan Q, Luo X, Chegini N. Differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids. J Cell Mol Med. 2008 Jan-Feb;12:227–240
  67. Nuovo GJ, Schmittgen TD. Benign metastasizing leiomyoma of the lung: clinicopathologic, immunohistochemical, and micro-RNA analyses. Diagn Mol Pathol. 2008;17:145–150
  68. Dinh TA, Oliva EA, Fuller AF, et al. The treatment of uterine leiomyosarcoma. Results from a 10-year experience (1990–1999) at the Massachusetts General Hospital. Gynecol Oncol. 2004;92:648–652
  69. Giuntoli RL, Metzinger DS, DiMarco CS, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol. 2003;89:460–469
  70. Larson B, Silfversward C, Nilsson B, et al. Prognostic factors in uterine leiomyosarcoma. A clinical and histopathological study of 143 cases. The Radiumhemmet series 1936–1981. Acta Oncol. 1990;29:185–191
  71. Gadducci A, Landoni F, Sartori E, et al. Uterine leiomyosarcoma: analysis of treatment failures and survival. Gynecol Onco. 1996;62:25–32
  72. Mayerhofer K, Obermair A, Windbichler G, et al. Leiomyosarcoma of the uterus: a clinicopathologic multicenter study of 71 cases. Gynecol Oncol. 1999;74:196–201
  73. Wu TI, Chang TC, Hsueh S, et al. Prognostic factors and impact of adjuvant chemotherapy for uterine leiomyosarcoma. Gynecol Oncol. 2006;100:166–172
  74. D’Angelo E, Spagnoli LG, Prat J. Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system. Hum Pathol. 2009;40:1571–1585
  75. Pelmus M, Penault-Llorca F, Guillou L, et al. Prognostic factors in early-stage leiomyosarcoma of the uterus. Int J Gynecol Cancer. 2009;19:385–390
  76. Abeler VM, Royne O, Thoresen S, et al. Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology. 2009;54:355–364
  77. Evans HL, Chawla SP, Simpson C, et al. Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors. Cancer. 1988;62:2239–2247
  78. D’Angelo E, Prat J. Uterine sarcomas: a review. Gynecol Oncol. 2010;116:131–139
  79. Kempson RL. Sarcomas and related neoplasms. In:  Norris HJ,  Hertig AT,  Abell MR editor. The uterus. Baltimore: Williams & WIlkins; 1973;
  80. Taylor HB, Norris HJ. Mesenchymal tumors of the uterus. IV. Diagnosis and prognosis of leiomyosarcomas. Arch Pathol. 1966;82:40–44
  81. Downes KA, Hart WR. Bizarre leiomyomas of the uterus: a comprehensive pathologic study of 24 cases with long-term follow-up. Am J Surg Pathol. 1997;21:1261–1270
  82. Prayson RA, Hart WR. Mitotically active leiomyomas of the uterus. Am J Clin Pathol. 1992;97:14–20
  83. Guntupalli SR, Ramirez PT, Anderson ML, et al. Uterine smooth muscle tumor of uncertain malignant potential: a retrospective analysis. Gynecol Oncol. 2009;113:324–326
  84. Rosai J. Uterus - corpus. In:  Rosai J editors. Rosai and Ackerman’s surgical pathology. 9th ed.. New York: Mosby; 2004;p. 1612
  85. Longacre TA, Atkins KA, Kempson RL, et al. The uterine corpus. In:  Mills SE editors. Sternberg’s diagnostic surgical pathology. 5th ed.. Baltimore: Lippincott Williams and Wilkins; 2010;p. 2248–2277
  86. Oliva E. Pure mesenchymal and mixed Mullerian tumors of the uterus. In:  Nucci MR,  Oliva E editor. Gynecologic pathology. 1st ed.. Philadelphia: Churchill Livingstone Elsevier; 2009;p. 289
  87. Nucci MR. Tumors of female genital tract: myometrium. In:  Fletcher CD editors. Diagnostic histopathology of tumors. 3rd ed.. Philadelphia: Churchill Livingstone Elsevier; 2007;p. 690–692
  88. Quade BJ, Robboy SJ. Uterine smooth muscle tumors. In:  Robboy SJ,  Mutter GL,  Prat J editor. Pathology of the female reproductive tract. 2nd ed.. Philadelphia: Churchill Livingstone Elsevier; 2009;p. 463
  89. Zaloudek CJ, Hendrickson MR, Soslow RA. Mesenchymal tumors of the uterus. In:  Kurman RJ,  Ellenson LH,  Ronnett BM editor. Blaustein’s pathology of the female genital tract. 6th ed.. New York: Springer; 2011;p. 455–477
  90. Berretta R, Rolla M, Merisio C, et al. Uterine smooth muscle tumor of uncertain malignant potential: a three-case report. Int J Gynecol Cancer. 2008;18:1121–1126
  91. Sung CO, Ahn G, Song SY, et al. Atypical leiomyomas of the uterus with long-term follow-up after myomectomy with immunohistochemical analysis for p16INK4A, p53, Ki-67, estrogen receptors, and progesterone receptors. Int J Gynecol Pathol. 2009;280:529–534
  92. Przybora LA. Leiomyosarcoma in situ of the uterus. Cancer. 1961;14:483–492
  93. Ly A, McKenney JK, Longacre TA, et al. Atypical leiomyoma of the uterus: a clinicopathologic study of 46 cases [abstract]. Mod Pathol. 2009;22:225A
  94. Veras E, Malpica A, Deavers MT, et al. Mitosis-specific marker phospho-histone H3 in the assessment of mitotic index in uterine smooth muscle tumors: a pilot study. Int J Gynecol Pathol. 2009;28:316–321
  95. O’Neill CJ, McCluggage WG. p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol. 2006;13:8–15
  96. Lee CH, Turbin DA, Sung YC, et al. A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors. Mod Pathol. 2009;22:1519–1531
  97. Unver NU, Acikalin MF, Oner U, et al. Differential expression of P16 and P21 in benign and malignant uterine smooth muscle tumors. Arch Gynecol Obstet. 2010;[Epub ahead of print]
  98. Chen L, Yang B. Immunohistochemical analysis of p16, p53, and Ki-67 expression in uterine smooth muscle tumors. Int J Gynecol Pathol. 2008;27:326–332
  99. Peters WA, Howard DR, Andersen WA, et al. Uterine smooth-muscle tumors of uncertain malignant potential. Obstet Gynecol. 1994;83:1015–1020
  100. Esposito NN, Hunt JL, Bakker A, et al. Analysis of allelic loss as an adjuvant tool in evaluation of malignancy in uterine smooth muscle tumors. Am J Surg Pathol. 2006;30:97–103
  101. Scurry J, Kerdemelidis P, Fortune D. Small atypical leiomyomas: report of two cases. Pathology. 2001;33:319–321
  102. Amant F, Moerman P, Vergote I. Report of an unusual problematic uterine smooth muscle neoplasm, emphasizing the prognostic importance of coagulative tumor cell necrosis. Int J Gynecol Cancer. 2005;15:1210–1212
  103. Shapiro A, Ferenczy A, Turcotte R, et al. Uterine smooth-muscle tumor of uncertain malignant potential metastasizing to the humerus as a high-grade leiomyosarcoma. Gynecol Oncol. 2004;94:818–820
  104. Amada S, Nakano H, Tsuneyoshi M. Leiomyosarcoma versus bizarre and cellular leiomyomas of the uterus: a comparative study based on the MIB-1 and proliferating cell nuclear antigen indices, p53 expression, DNA flow cytometry, and muscle specific actins. Int J Gynecol Pathol. 1995;14:134–142
  105. Ng JS, Han A, Chew SH, et al. A clinicopathologic study of uterine smooth muscle tumours of uncertain malignant potential (STUMP). Ann Acad Med Singapore. 2010;39:625–628

PII: S1521-6934(11)00107-6

doi: 10.1016/j.bpobgyn.2011.07.003

Best Practice & Research Clinical Obstetrics & Gynaecology
Volume 25, Issue 6 , Pages 691-704 , December 2011