A Look at Uterine Wound Healing Through a Histopathological Study of Uterine Scars

Background Few histopathologic studies of uterine wound healing have been published compared with similar healing in other tissues. Our objective was to examine the histopathology resulting from iatrogenic trauma to the myometrium to acquire a better understanding of possible aberrations in uterine wound healing.

We studied paired injured myometrium and uninvolved myometrium from 7 hysterectomy specimens. All subjects had either abnormal bleeding or chronic pain following an iatrogenic injury to the myometrium. The time between the initial injury and hysterectomy ranged from 2 months to 13 years. Tissue was evaluated with hematoxylin and eosin (H&E) followed by Masson Trichrome staining for collagen, Weigert-Van Gieson elastic staining, and/or Kreyberg staining for fibrin and glycosaminoglycans or MIB-1 (Ki-67) immunhistochemistry for cell proliferation.

Histopathologic examination of the 7 paired tissues revealed evidence of altered healing including myofiber disarray, elastosis, tissue edema, and inflammation. Small fibroids, myometrial hyperplasia, a keloid-like region of scar and adenomyosis were also observed.

Myofiber disarray and elastosis may be markers of aberrancy in wound healing after iatrogenic uterine trauma. Altered myometrial scarring in these cases may have contributed to the clinical outcome necessitating hysterectomies. Myometrial hyperplasia in the region of the scars might also contribute to the clinical presentation as well. Small fibroids found within scars and evidence of a keloid-like structure may also represent alterations in uterine wound healing. Similar content being viewed by others

Wang J, Ding J, Jiao H, et al. Human hypertrophic scar-like nude mouse model characterization of the molecular and cellular biology of the scar process. Wound Repair Regen. 2011;19(2):274–285. Russell SB, Russell JD, Trupin KM, et al. Epigentically altered wound healing in keloid fibroblasts. J Invest Dernatol. 2010;130(10):2489–2496. Deshpande MS, Kuchroo PV. A novel dermal tissue construct: development and in vitro characterization. Biotechnol Prog. 2010;26(5):1424–1430. Vaginal Birth after Previous Cesarean Delivery. Practice Bulletin No. 115. American college of obstetricians and gynecologists. Obstet Gynecol. 2010;116(2 pt 1):450–463. Spong CY, Queenan JT. Uterine scar assessment: how should it be done before trial of labor after cesarean delivery? Obstet Gynecol. 2011;117(3):521–522. Vikhareva Osser O, Valentin L. Clinical importance of appearance of cesarean hysterotomy scar at transvaginal ultrasonography in nonpregnant women. Obstet Gynecol. 2011;117(3):525–533. Leyendecker G, Wildt L, Mall G. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet. 2009;280(4):529–538. Leppert PC, Catherino WH, Segars JH. A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays. Am J Obstet Gynecol. 2006;195(2):415–420. Catherino WH, Leppert PC, Stenmark MH. Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloid. Genes Chromosomes Cancer. 2004;40(3):204–217. Leppert PC, Baginski T, Prupas C, Catherino WH, Pletcher S, Segars JH. Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium. Fertil Steril. 2004;82(3):1182–1187. Cramer SF, Mann L, Calianese E, Daley J, Wiliamson K. Association of seedling myomas with myometrial hyperplasia. Hum Pathol. 2009;40(2):218–225. El-Zammar O, Rosenbuam P, Katzenstein AL. Proliferative activity in fibrosising lung diseases: a comparative study of Ki-67 immunoreactivity in diffuse alvelolar damage, bronchiolitis obliterans-organizing pneumonia, and usual interstitial pneumonia. Hum Pathol. 2009;40(8):1182–1188. Cramer SF, Patel A. Myometrial hyperplasia: proposed criteria for a discrete morphological entity. Mod Pathol. 1995;8(1):71–77. Weedon D. Pathology of the Skin. Churchill Livingstone: New York, NY; 1997:298–299. Colgan TJ, Shah R, Leyland N. Post-hysteroscopic ablation reaction-a histopathologic study of the effects of the electrosurgical ablation. Int J Gyn Path. 1999;18(4):325–331. Buhimschi CS, Buhimschi IA, Yu C, et al. The effect of dystocia and previous cesarean uterine scar on the tensile properties of the lower uterine segment. Am J Obstet Gynecol. 2006;194(3):873–883. Buhimschi CS, Buhimschi IA, Patel S, Malinow AM, Weiner CP. Rupture of the uterine scar during term labour: contractility or biochemistry? BJOG. 2005;112(1):38–42. Buhimschi CS, Zhao G, Sora N, Madri J, Buhimschi IA. Myometrial wound healing post-Cesaarean delivery in the MRL/Mpj mouse model of uterine scarring. Am J Pathol. 2010;177(1):197–207. McCulloch TA, Wagner B, Duffy S, Barik S, Smith JHF. The pathology of hysterectomy specimens following trans-cervical resection of the endometrium. Histopathology. 1995;27(6):541–547. Fadare O, Qin L, Martel M, Tavassoli FA. Pathology of novasure endometrial ablation system. Arch Path Lab Med. 2005;129(9):1175–1178. Fadare O, Wang SA, Renshaw IL. Does the radiofrequency impedance controlled endometrial ablation have any morphological effects on uterine leiomyoma? Diagn Pathol. 2008;3:28–30. Midwood KS, Williams LV, Schwarzbauer JT. Tissue repair and the dynamics of the extracellular matix. Int J Biochem Cell Biol. 2004;36(6):1031–1037. Cramer SF, Newcomb PM, Bonfiglio TA. Myometrial dysplasia (atypical myometrial hyperplasia). Hum Pathol. 2007;38(4):652–655. Cramer SF, Meyer JA, Kraner JF, Camel M, Mazur MT, Tenen-baum MS. Metastasizing leiomyoma of the uterus-S-phase fraction, estrogen receptor and ultrastructure. Cancer. 1980;45(5):932–937. 21. Eaglstein WH, Falanga V. Chronic wounds. Surg Clin North Am. 1997;77(3):689–700. Goldberg SR, Diegelmann RF. Wound healing primer. Surg Clin North Am. 2010;90(6):1133–1146. Knoch S, Price P. Cellular, molecular and biochemical differences in the pathophysiology of healing between acute wounds, chronic wounds and wounds in the elderly. 2004. Worldwide-wounds.com. Robboy SJ, Mutter GL, Prat J, et al. Robboy’s Pathology of the Female Reproductive tract. 2nd ed. New York, NY: Churchill Livingstone; 2009. Silver MD, Gotleib AI, Schoen FJ. Cardivascular Pathology. 3rd ed. New York, NY: Churchill Livingstone; 2001. Robinson BK. Grobman: effectiveness of timing strategies for delivery of individual with placenta previa and accreta. Obstet Gynecol. 2010;116(4):835–842. Warshak CR, Ramos GA, Eskander R, et al. Effect of predelivery diagnosis in 99 consecutive cases of placenta accreta. Obstet Gynecol. 2010;115(1):65–69. Schwalm H, Dubrauszky V. The structure of the musculature of the human uterus–muscles and connective tissue. Am J Obstet Gynecol. 1966;95(3):391–399. Uitto J. The role of elastin and collagen in cutaneous aging: instrinsic aging versus photoexposure. J Drugs Dermatol. 2008;7(2 suppl):s12–s16. Brian West A. The pathology of diverticulosis: classical concepts and mucosal changes in diverticula. J Clin Gastroentero. 2006; 40(suppl 3):S126–S131. Suarez-Mier MP, Fernandez-Simon L, Gawallo C. Pathologic changes of the cardiac conduction tissue in sudden cardiac death. Am J Forensic Med Pathol. 1995;16(3):193–202. Hayashi M, Mori Y, Nogami K, Takagi Y, Yaoi M, Ohkura T. A hypothesis to explain the occurrence of massive postpartum hemorrhage. Acta Obstet Gynecol Scand. 2000;79(2):99–106. Yousem SA. Pulmonary apical cap. A distinctive but poorly recognized lesion in pulmonary surgical pathology. Am J Surg Pathol. 2001;25(5):679–683. Tregson-Roberts G, Hanley SA, Roberts JT. Myometrial vascular damage after surgical sterilization by tubal diathermy. J Clin Pathol. 1978;31(7):633–638. Leppert PC, Yu SY. Three-dimensional structures of uterine elastic fibers: scanning electron microscopic studies. Connect Tissue Res. 1991;27(1):15–31. Metaxa-Mariatou V, McGavigan CJ, Robertson K, Stewart C, Cameron IT, Campbell S. Elastin distribution in the myometrial and vascular smooth muscle of the human uterus. Mol Hum Reprod. 2002;8(6):559–565. Zheng WQ, Ma R, Zheng JM, Gong ZJ. Elastin distribution in the normal uterus, uterine leiomyomas, adenomyosis and adenomyomas: a comparison. Anal Quant Cytol Histol. 2006;28(2):115–120. Cramer SF, Padela AI, Marchetti CE, Newcomb PM, Heller DS. Myometrial hyperplasia in pediatric, adolescent and young adult uteri. J Pediatr Adolesc Gynecol. 2003;16(5):301–306. Cramer SF, Horiszny JA, Leppert P. Epidemiology of uterine leiomyomoas. With an etiologic hypothesis. J Reprod Med. 1995;40(8):595–600. Cramer SF, Ng T, Paulot P., Leppert PC. Myometrial Hyperplasia (MMH), a Precursor of Fibroids, in Hysterectomies for Benign Disease. Advances in Uterine Leiomyoma Research 3 rd NIH International Congress. PA45 ORWH, NIH. November 22–23, 2010. Luo X, Pan Q, Liu L, Chegini N. Genomic and proteomic profiling II: comparative assessment of gene expression profiles in leiomyomas, keloids, and surgically-induced scars. Reprod Biol. 2007;5:35. doi 10.1186/1477-7827-5-35. Lewis PL, Lee ABH, Easler RE. Myometrial hypertrophy-a clinical pathologic study and review of the literature. Am J Obstet Gynecol. 1962;84:1032–1041. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Roeder, H.A., Cramer, S.F. & Leppert, P.C. A Look at Uterine Wound Healing Through a Histopathological Study of Uterine Scars. Reprod. Sci. 19, 463–473 (2012). https://doi.org/10.1177/1933719111426603 Published: Issue date: DOI: https://doi.org/10.1177/1933719111426603