Skip to main content Accessibility help
  • Print publication year: 2012
  • Online publication date: July 2013

12 - Uterine smooth muscle tumors



Uterine leiomyomas are the most common mesenchymal tumor in the female genital tract; the vast majority are easily diagnosed. Most uterine leiomyosarcomas, although much less common, are also readily diagnosed. Diagnostic problems arise when uterine mesenchymal tumors exhibit (1) altered or non-standard forms of smooth muscle differentiation (myxoid, epithelioid, etc.), (2) variant or ambiguous histologic features (e.g., increased cellularity, cytologic atypia, increased mitotic figures, or necrosis), (3) a mixture of smooth muscle and stromal differentiation, or (4) unusual anatomic distribution.

The diagnosis of uterine smooth muscle tumors depends on: the degree of experience with that entity (i.e., uterine leiomyomas are very common and, therefore, histologic criteria are well defined and well recognized for the vast majority of these tumors); the extent to which the specimen under evaluation is representative of the entire tumor (a particular issue with uterine samplings and myomectomy specimens); and the extent to which the tumor exhibits non-ambiguous morphologic or anatomical distributional features. Uterine smooth muscle tumors that are rarely encountered and therefore have less reported clinical follow-up data are often more correctly referred to as “with limited experience,” while those that defy classification using standard criteria are more appropriately labeled as “uncertain malignant potential.” Most uterine tumors of “uncertain malignant potential” may prove, over time and accumulated experience, to have low recurring potential (recurrences to local pelvic or intra-abdominal sites) or low malignant potential (delayed metastases to lung, bone, etc., with prolonged clinical course following excision of the metastases – i.e.

Bell, SW, Kempson, RL, Hendrickson, MR.Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol 1994;18:535–58.
Mills, AM, Longacre, TA.Smooth muscle tumors of the female genital tract. Surg Pathol Clin 2009;2(4):625–77.
Wang, X, Kumar, D, Seidman, JD.Uterine lipoleiomyomas: a clinicopathologic study of 50 cases. Int J Gynecol Pathol 2006;25:239–42.
Chen, KT.Uterine leiomyohibernoma. Int J Gynecol Pathol 1999;18:96–7.
McCluggage, WG, Boyde, A.Uterine angioleiomyomas: a report of 3 cases of a distinctive benign leiomyoma variant. Int J Surg Pathol 2007;15:262–5.
Myles, J, Hart, W.Apoplectic leiomyomas of the uterus. A clinicopathologic study of five distinctive hemorrhagic leiomyomas associated with oral contraceptive usage. Am J Surg Pathol 1985;9:798–805.
Parker, RL, Young, RH, Clement, PB.Skeletal muscle-like and rhabdoid cells in uterine leiomyomas. Int J Gynecol Pathol 2005;24:319–25.
Dundr, P, Povysil, C, Tvrdik, D, et al. Uterine leiomyomas with inclusion bodies: an immunohistochemical and ultrastructural analysis of 12 cases. Pathol Res Pract 2007;203:145–51.
Ferry, JA, Young, RH.Malignant lymphoma, pseudolymphoma, and hematopoietic disorders of the female genital tract. Pathol Annu 1991;26:227–63.
Roth, LM, Reed, RJ.Dissecting leiomyomas of the uterus other than cotyledonoid dissecting leiomyomas: a report of eight cases. Am J Surg Pathol 1999;23:1032–9.
Ly, A, McKenney, TA, Longacre, TA, et al. Atypical leiomyomas of the uterus: a clinicopathologic study of 46 cases. Mod Pathol 2009;22:225A.
Clement, P, Young, R, Scully, R.Diffuse, perinodular, and other patterns of hydropic degeneration within and adjacent to uterine leiomyomas. Problems in differential diagnosis. Am J Surg Pathol 1992;16:26–32.
Prayson, RA, Goldblum, JR, Hart, WR.Epithelioid smooth-muscle tumors of the uterus: a clinicopathologic study of 18 patients. Am J Surg Pathol 1997;21:383–91.
Hendrickson, MR, Longacre, TA, Kempson, RL.Pathology of uterine sarcomas. In: Rubin, SC, Coukos, G, eds. Cancer of the Uterus. New York: Publishers Domain; 2004:149–94.
Longacre, TA, Atkins, KA, Kempson, RL, et al. The uterine corpus. In: Sternberg, S, Mills, S, eds. Diagnostic Surgical Pathology. New York: Raven Press; 2009:2203–305.
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.
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.
Nucci, MR, O'Connell, JT, Huettner, PC, et al. h-Caldesmon expression effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors. Am J Surg Pathol 2001;25:455–63.
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;26:403–12.
Cramer, SF, Mann, L, Calianese, E, et al. Association of seedling myomas with myometrial hyperplasia. Hum Pathol 2009;40:218–25.
Laskin, WB, Fetsch, JF, Tavassoli, FA.Superficial cervicovaginal myofibroblastoma: fourteen cases of a distinctive mesenchymal tumor arising from the specialized subepithelial stroma of the lower female genital tract. Hum Pathol 2001;32:715–25.
Kaminski, P, Tavassoli, F.Plexiform tumorlet: a clinical and pathologic study of 15 cases with ultrastructural observations. Int J Gynecol Pathol 1984;3:124–34.
Clement, P, Scully, R.Uterine tumors resembling ovarian sex-cord tumors. A clinicopathologic analysis of fourteen cases. Am J Clin Pathol 1976;66:512–25.
Hildebrandt, RH, Rouse, RV, Longacre, TA.Value of inhibin in the identification of granulosa cell tumors of the ovary. Hum Pathol 1997;28:1387–95.
Irving, JA, Carinelli, S, Prat, J.Uterine tumors resembling ovarian sex cord tumors are polyphenotypic neoplasms with true sex cord differentiation. Mod Pathol 2006;19:17–24.
Veras, E, Zivanovic, O, Jacks, L, Chiappetta, D, Hensley, M, Soslow, R. “Low-grade leiomyosarcoma” and late-recurring smooth muscle tumors of the uterus: a heterogenous collection of frequently misdiagnosed tumors associated with an overall favorable prognosis relative to conventional uterine leiomyosarcomas. Am J Surg Pathol. 2011;35(11):1626–37.
,FIGO staging for uterine sarcomas. FIGO Committee on Gynecologic Oncology. Int J Gynecol Obstet 2009;104:179.
Atkins, K, Bell, S, Kempson, RL, et al. Myxoid smooth muscle neoplasms of the uterus. Mod Pathol 2001;14:132A.
Kim, YH, Cho, H, Kyeom, KH, et al. Uterine endometrial stromal sarcoma with rhabdoid and smooth muscle differentiation. J Korean Med Sci 1996;11:88–93.
Atkins, K, Bell, S, Kempson, RL, et al. Epithelioid smooth muscle neoplasms of the uterus. Mod Pathol 2001;14:132A.
O'Neill, CJ, McBride, HA, Connolly, , 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;50:851–8.
Ferguson, SE, Gerald, W, Barakat, RR, et al. Clinicopathologic features of rhabdomyosarcoma of gynecologic origin in adults. Am J Surg Pathol 2007;31:382–9.
McCluggage, WG, Lioe, TF, McClelland, HR, et al. Rhabdomyosarcoma of the uterus: report of two cases, including one of the spindle cell variant. Int J Gynecol Cancer 2002;12:128–32.
Rabban, JT, Zaloudek, CJ, Shekitka, KM, et al. Inflammatory myofibroblastic tumor of the uterus: a clinicopathologic study of 6 cases emphasizing distinction from aggressive mesenchymal tumors. Am J Surg Pathol 2005;29:1348–55.
Terada, T.Gastrointestinal stromal tumor of the uterus: a case report with genetic analyses of c-kit and PDGFRA genes. Int J Gynecol Pathol 2009;28:29–34.
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.
Baergen, RN, Rutgers, JL, Young, RH, et al. Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 2006;100:511–20.
Shih, IM, Kurman, RJ.Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 1998;22:1393–403.
Shih, IM, Kurman, RJ.p63 expression is useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations. Am J Surg Pathol 2004;28:1177–83.
McCluggage, WG, Young, RH.Myxoid change of the myometrium and cervical stroma: description of a hitherto unreported non-neoplastic phenomenon with discussion of myxoid uterine lesions. Int J Gynecol Pathol 2010;29:351–7.
Yanai, H, Wani, Y, Notohara, K, et al. Uterine leiomyosarcoma arising in leiomyoma: clinicopathological study of four cases and literature review. Pathol Int 2010;60:506–9.
Lillemoe, TJ, Perrone, T, Norris, HJ, et al. Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas. Arch Pathol Lab Med 1991;115:215–19.
Oliva, E, Clement, PB, Young, RH, et al. Mixed endometrial stromal and smooth muscle tumors of the uterus: a clinicopathologic study of 15 cases. Am J Surg Pathol 1998;22:997–1005.
Hales, HA, Peterson, CM, Jones, KP, Quinn, JD.Leiomyomatosis peritonealis disseminata treated with a gonadotropin-releasing hormone agonist. A case report [published erratum appears in Am J Obstet Gynecol 1993;169(2 Pt 1):439]. Am J Obstet Gynecol 1992;167:515–16.
Arif, S, Ganesan, R, Spooner, D.Intravascular leiomyomatosis and benign metastasizing leiomyoma: an unusual case. Int J Gynecol Cancer 2006;16:1448–50.
Kayser, K, Zink, S, Schneider, T, et al. Benign metastasizing leiomyoma of the uterus: documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases. Virchows Arch 2000;437:284–92.
Nucci, MR, Drapkin, R, Dal Cin, P, et al. Distinctive cytogenetic profile in benign metastasizing leiomyoma: pathogenetic implications. Am J Surg Pathol 2007;31:737–43.
Clement, P, Young, R, Scully, R.Intravenous leiomyomatosis of the uterus. A clinicopathological analysis of 16 cases with unusual histologic features. Am J Surg Pathol 1988;12:932–45.
Quade, BJ, Dal Cin, P, Neskey, DM, et al. Intravenous leiomyomatosis: molecular and cytogenetic analysis of a case. Mod Pathol 2002;15:351–6.
Dal Cin, P, Quade, BJ, Neskey, DM, et al. Intravenous leiomyomatosis is characterized by a der(14)t(12;14)(q15;q24). Genes Chromosomes Cancer 2003;36:205–6.
Gyure, KA, Hart, WR, Kennedy, AW.Lymphangiomyomatosis of the uterus associated with tuberous sclerosis and malignant neoplasia of the female genital tract: a report of two cases. Int J Gynecol Pathol 1995;14:344–51.
Longacre, TA, Hendrickson, MR, Kapp, DS, et al. Lymphangioleiomyomatosis of the uterus simulating high-stage endometrial stromal sarcoma. Gynecol Oncol 1996;63:404–10.
Weiss, SW.Smooth muscle tumors of soft tissue. Adv Anat Pathol 2002;9:351–9.
Larrain, D, Rabischong, B, Khoo, CK, et al. “Iatrogenic” parasitic myomas: unusual late complication of laparoscopic morcellation procedures. J Minim Invasive Gynecol 2010;17:719–24.
Nezhat, C, Kho, K.Iatrogenic myomas: new class of myomas?J Minim Invasive Gynecol 2010;17:544–50.
Wei, MH, Toure, O, Glenn, GM, et al. Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet 2006;43:18–27.
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;29:1558–75.
Fadare, O, Parkash, V, Yilmaz, Y, et al. Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal “PEComatosis”: a clinicopathological study with comparative genomic hybridization analysis. World J Surg Oncol 2004;2:35.
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.
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.
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;28:244–9.
Simpson, KW, Albores-Saavedra, J.HMB-45 reactivity in conventional uterine leiomyosarcomas. Am J Surg Pathol 2007;31:95–8.