Uterine sarcomas in South African black women: a clinicopathologic study with ethnic considerations

Background: There is considerable evidence for a higher incidence of uterine sarcomas in blacks when compared to whites. However, whether this higher incidence is related to differences in clinicopathologic presentation is not known.

Patients and methods: We reviewed slides and clinical charts of 81 patients with a primary diagnosis of uterine sarcoma referred between 1991 and 1999 to Kalafong Academic and Pretoria Academic Hospital. After review, 49 cases remained for study.

Results: Uterine sarcomas were distributed between leiomyosarcoma (LMS) (39%), carcinosarcoma (CS) (49%) and endometrial stromal sarcoma (ESS) (12%). LMS and ESS tend to present at an earlier age when compared to CS (respectively p < 0.008 and 0.02). Of women with LMS more women are premenopausal when compared to CS (p < 0.009). Lower abdominal pain is more common in LMS (p < 0.009), whereas bleeding is more common in women suffering from CS (p < 0.01). Lymphovascular space involvement and cervical involvement are more common in CS when compared to LMS. In CS, the carcinoma component has most of the metastatic potential.

Conclusion: Among black South African women different clinicopathologic features for uterine LMS, CS and ESS are observed. We also present genetic and/or hormonal factors possibly contributing to the pathophysiology of uterine sarcomas in blacks.

Uterine sarcoma; Leiomyosarcoma; Carcinosarcoma; Endometrial stromal sarcoma; Race; Ethnic

[1] Powell l.J., Banerjee M., Sakr W. et al.: "Should African-American men be tested for prostate carcinoma at an earlier age than white men?" Cancer, 1999, 85, 472.

[2] Troisi R.J., Freedman A.N., Devesa S.S.: "Incidence of colorectal carcinoma in the US. An update of trends by gender, race, age, subsite and stage, 1975-1994". Cancer, 1999, 85, 1670.

[3] Newman L.A., Alfonso A.E.: "Age-related differences in breast cancer stage at diagnosis between black and white patients in an urban community hospital". Ann. Surg. Oncol., 1997, 4(8), 655.

[4] Cramer D.W., Cutler S.J.: "Incidence and histopathology of malignancies of the female genital organs in the United States". Am. J. Obstet. Gynecol., 1974, 118, 443.

[5] Bain R.P., Greenberg R.S., Chung K.C.: "Racial differences in survival of women with endometrial cancer". Am. J. Obstet. Gynecol., 1987, 157, 914.

[6] Zaloudek C., Nonis H.J.: "Mesenchymal tumors of the uterus". In: Kurrnan R.J., ed. Blaustein's Pathology of the Female Genital Tract. New-York: Springer-Verlag, fourth edition, 1994, 487.

[7] Disaia P.J., Creasman W.T.: "Sarcoma of the uterus". In: Disaia P.J., Creasman W.T., eds. Clinical Gynecologic Oncology. St. Louis, Missouri: Mosby, fifth edition, 1997, 169.

[8] Christopherson W.M., Williamson E.0., Gray L.A.: "Leiomyosarcoma of the uterus". Cancer, 1972, 29, 1512.

[9] Harlow B.L., Weiss N.S., Lofton S.: "The epidemiology of sarcomas of the uterus". J. Natl. Cancer inst., 1986, 76(3), 399.

[10] Schwartz S.M., Weiss N.S., Daling J.R. et al.: "Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus". Cancer, 1996, 77(4), 717.

[11] Williamson E.0., Christopherson W.M.: "Malignant mixed miillerian tumours of the uterus". Cancer, 1972, 29, 585.

[12] Zelmanowics A., Hildesheim A., Sherman M.E. et al.: "Evidence for a common etiology for endometrial carcinomas and malignant mixed Miillerian tumors". Gynecol. Oncol., 1998, 69, 253.

[13] Bell S.W., Kempson R.L., Hendrickson M.R.: "Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases". Am. J. Surg. Pathol., 1994, 18(6), 535.

[14] Hrynchak M., Horsman D., Salski C., Berean K., Benedet J.L.: "Complex karyotypic alterations in an endometrial stromal sarcoma". Cancer Genet. Cytogenet.,1994, 77, 45.

[15] Laxman R., Currie J.L., Kurman R.J., Dudzinski M., Griffin C.A.: "Cytogenetic profile of uterine sarcomas". Cancer, 1993, 71(4), 1283.

[16] Nilbert M., Mandahl N., Heim S. et al.: "Complex karyotypic changes, including rearrangements of 12q l 3 and 14q24, in two leiomyosarcomas". Cancer Genet. Cytogenet., 1990, 48, 217.

[17] Dal Cin P., Boghosian L., Crickard K., Sandberg A.A.: "T(10;17) as the sole chromosome change in a uterine leiomyosarcoma". Cancer Genet. Cytogenet., 1988, 32, 263.

[18] Dal Cin P.,Talcott J., Abrams J., Li F.P., Sandberg A.A.: "Ins( l 0;19) in an endometrial stromal sarcoma". Cancer Genet. Cytogenet., 1988, 36, 1.

[19] Shields P.G., Caporaso N.E., Falk R.T. et al.: "Lung cancer, race, and a CYPIAI genetic polymorphism". Cancer Epidemiology, Biomarkers & Prevention, 1993, 2(5), 481.

[20] Bhatia K.G., Cherney B.W., Huppi K. et al.: "A deletion linked to a poly(ADP-ribose) polymerase gene on chromosome 13q33-qter occurs frequently in the normal black population as well as in multiple tumor DNA". Cancer Res., 1990, 50, 5406.

[21] Lyn D., Cherney B.W., Lalande M. et al.: "A duplicated region is responsible for the poly(ADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer". Am. J. Hum. Genet., 1993, 52(1), 124.

[22] Little C.D., Nau M.M., Carney D.N., Gazdar A.F., Minna J.D.: "Amplification and expression of the c-myc oncogene in human lung cancer cell lines". Nature, 1983, 306, 194.

[23] Riou G., Le M.G., Le Doussal V., Barrois M., George M., Haie C.: "C-myc proto-oncogene expression and prognosis in early carcinoma of the uterine cervix". Lancet, 1987, 8536, 761.

[24] De Vos S., Wilczynski S.P., Fleishhacker M., Koeffler P.: "p53 alterations in uterine leiomyosarcomas versus leiomyomas". Gynecol. Oncol., 1994, 54, 205.

[25] Jeffers M.D., Farquharson M.A., Richmond J.A., McNicol M.: "p53 immunoreactivity and mutation of the p53 gene in smooth muscle tumours of the uterine corpus". J. Pathol., 1995, 177, 65.

[26] Liu F.-S., Kohler M.F., Marks J.R., Bast R.C., Boyd J., Berchuck A.: "Mutation and overexpression of the P53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas". Obstet. Gynecol., 1994, 83, 118.

[27] Nordal R.R., Kristensen G.B., Stenwig A.E., Trope C.G., Nesland J.M.: "lmmunohistochemical analysis of p53 protein in uterine sarcomas". Gynecol. Oneal., 1998, 70, 45.

[28] Kohler M.F., Carney P., Dodge R. et al.: "P53 overexpression in advanced-stage endometrial adenocarcinoma". Am. J. Obstet. Gynecol., 1996, 175, 1246.

[29] Quade B.J., Pinto A.P., Howard D.R., Peters W.A., Crum C.P.: "Frequent loss of heterozygosity for chromosome 10 in uterine leiomyosarcoma in contrast to leiomyoma". Am. J. Path., 1999, 154, 945.

[30] Steck P.A., Pershouse M.A., Jasser S.A. et al.: "Identification of a candidate tumour suppressor gene, MMAC I, at chromosome 10q23.3 that is mutated in multiple advanced cancers". Nat. Genet., 1997, 15, 356.

[31] Bradlow H.L., Davis D.L., Lin G., Sepkovic D.W., Timari R.: "Effects of pesticides on the ratio of 16-hydroxyestrone: a biologic marker of breast cancer risk". Environ. Health. Perspect., 1995, 103, 147.

[32] Davis D.L., Bradlow H.L., Wolff M., Woodruff T., Hoel D.G., Anton-Culver H.: "Medical hypothesis: xenoestrogens as preventable causes of breast cancer". Environ. Health Perspect., 1993, 101, 372.

[33] Taioli E., Garte S.J., Trachman J. et al.: "Ethnic differences in estrogen metabolism in healthy women". J. Natl. Cancer Inst.,1996, 88(9), 617.

[34] Woods M.N., Barnett J.B., Spiegelman D. et al.: "Hormone levels during dietary changes in premenopausal African-American women". J. Nat. Cancer Inst., 1996, 88(19), 1369.

[35] Altaras M.M., Jaffe R., Cohen I., Gruber A., Yanai-lnbar I., Bernheim J.: "Role of prolonged excessive estrogen stimulation in the pathogenesis of endometrial sarcomas: two cases and a review of the literature". Gynecol. Oneal., 1990, 38, 273.

[36] Press M.F., Scully R.E.: "Endometrial'sarcomas' complicating ovarian thecoma, polycystic ovarian disease and estrogen therapy". Gynecol. Oneal., 1985, 21, 135.

[37] Bekkers R.L., Massuger L.F., van der Berg P.P., van Haelst U.G., Bulten J.: "Uterine malignant leiomyoblastoma (epihelioid leiomyosarcoma) during pregnancy". Gynecol. Oneal., 1999, 72, 433.

[38] Briand P., Hou-Jensen K., Thorpe S.M., Rose C.: "Hormonedependent uterine sarcomas in GR mice". Eur. J. Cancer, 1981, 17(6), 635.

[39] Beer T.W., Buchanan R., Buckley C.H.: "Uterine stromal sarcoma following tarnoxifen treatment". J. Clin. Path., 1995, 48, 596.

[40] Eddy G.L., Mazur M.T.: "Endolymphatic stromal myosis associated with tamoxifen use". Gynecol. Oneal., 1997, 64(2), 262.

[41] Altaras M.M.,A virarn R.,C ohen I.,C ordoba M.,Y arkoni S.,Beyth Y.: "Role of prolonged stimulation of tamoxifen therapy in the etiology of endometrial sarcomas". Gynecol. Oneal., 1993, 49, 255.

[42] Clarke M.R.: "Uterine malignant mixed Mullerian tumor in a patient on long-term tamoxifen therapy for breast cancer". Gynecol. Oncol., 1993, 51, 411.

[43] Clement P.B., Oliva E., Young R.H.: "Mullerian adenosarcoma of the uterine corpus associated with tamoxifen therapy: a report of six cases and a review of tamoxifen-associated endometrial lesions". Int. J. Gynecol. Path., 1996, 15, 222.

[44] Sasco A.J., Raffi F., Satge D., Goburdhun J., Fallouh B., Leduc B.: "Endometrial mullerian carcinosarcoma after cessation of tarnoxifen therapy for breast cancer". Int. J. Gynecol. Obstet., 1995, 48, 307.

[45] Seoud M., Johnson J., Weed J.C.: "Gynecologic tumors in tamoxifen-treated women with breast cancer". Obstet. Gynecol., 1993, 82, 165.

[46] Gillett D.: "Leiomyosarcoma of the uterus in a woman taking adjuvant tamoxifen therapy". Med. J. Aust., 1995, 163, 160.

[47] Loong E.P.,W ong F.W.: "Uterine leiomyosarcoma diagnosed during treatment with agonist of luteinizing hormone-releasing hormone for presumed uterine fibroid". Fertil. Steril., 1990, 54(3), 530.

[48] Mesia A.F., Williams F.S., Yan Z., Mittal K.: "Aborted le10myosarcoma after treatment with leuprolide acetate". Obstet. Gynecol., 1998, 92, 664.

[49] Kjerulff K.H., Langenberg P.L., Seidman J.D., Stolley P.D., Guzinsky G.M.: "Uterine leiomyomas. Racial d计ferences in severity, symptoms and age at diagnosis." J. Reprod. Med., 1996, 41, 483.

[50] Marshall L.M., Spiegelman D., Barbieri R.L. et al.: "Variation in the incidence of uterine leiomyoma among premenopausal women by age and race". Ohstet. Gynecol., 1997, 90(6), 967.

[51] Major F.J., Blessing J.A., Silverberg S.G. et al.: "Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study". Cancer, 1993, 71, 1702.

[52] Barter J.F., Smith E.B., Szpak C.A., Hinshaw W., Clarke-Pearson D.L., Creasman W.T.: "Leiomyosarcoma of the uterus: clinicopathologic study of 21 cases". Gynecol. Oneal., 1985, 21, 220.

[53] Kahanpaa K.V., Wahlstrom T., Grohn P., Heinonen E., Nieminen U., Widholm 0.: "Sarcomas of the uterus: a clinicopathologic study of 119 patients". Obstet. Gynecol., 1986, 67, 417.

[54] Larson B., Silfversward C., Nilsson B., Pettersson F.: "Prognostic factors in uterine leiomyosarcoma. A clinical and histopathological study of 143 cases. The Radiumhemmet series 1936-1981" Acta. Oneal., 1990, 29, 185.

[55] Olah K.S., Blunt S., Dunn J.A., Kelly K., Chan K.K.: "Retrospective analysis of 318 cases of uterine sarcoma". Eur. J. Cancer, 1991, 27(9), 1095.

[56] Macasaet M.A., Waxman M., F ruchter R.G. et al.: "Prognostic factors in malignant mesodermal (Mullerian) mixed tumors of the uterus". Gynecol. Oneal., 1985, 20, 32.

[57] Bitterman P., Byungkyu C., Kurrnan R.J.: "The significance of epithelial differentiation in mixed rnesoderrnal tumors of the uterus". Am. J. Surg. Path., 1990, 14(4), 317.

[58] Silverberg S.G., Major F.J., Blessing J.A. et al.: "Carcrnosarcorna (Malignant Mixed Mesoderrnal Tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases". Int. J Gynecol. Pathol., 1990, 9, 1.

[59] Meis J.M., Lawrence W.D.: "The immunohistochernical profile of malignant mixed Mullerian tumor". Am. J. Clin. Pathol., 1990, 94, 1.

[60] Rose P.O., Piver M.S., Tsukada Y., Lau T.: "Patterns of metastasis in uterine sarcoma. An autopsy study". Cancer, 1989, 63, 935.

[61] Fleming W.P., Peters W.A., Kumar N.B., Morley G.W.: "Autopsy findings in patients with uterine sarcoma". Gynecol. Oneal., 1984, 19, 168.

[62] Meredith R.F.,E isert D.R.,K aka Z.,H odgson S.E.,J ohnston G.A., Boutselis J.G.: "An excess of uterine sarcomas after pelvic irradiation". Cancer, 1986, 58, 2003.