Clinical and Reproductive Outcomes of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Tertiary Center Experience

Abstract

Some smooth muscle tumors do not meet the histologic criteria for definite benign-malignant distinction and this rare group is thus classified as smooth muscle tumors of uncertain malignant potential (STUMP). Due to the high heterogeneity, there are no standard guidelines for the diagnosis, treatment, and follow-up of uterine STUMPs. So, we aimed to evaluate the treatment modalities in patients with/without fertility desires. The size, mitotic count, presence of necrosis and atypia of tumors were obtained from the final pathology reports. Patients were followed up with electronically merged records via telephone until October 2022. Recurrence, time to recurrence, and recurrence histopathology were included in the study. Myomectomy was performed in 50% of the patients. Frozen section was not considered necessary in 57.1% of all patients and 50% of the patients who underwent frozen section were reported as benign. Median follow-up was 64.5 months. tumor necrosis was observed in 14.3% patients. The median mitosis count was calculated as 2.5 (1-9) per 10 high-power fields. Recurrence rate was calculated to be 7.2%. The accuracy of a frozen section diagnosis may not always be reliable, it is often confirmed after the final pathology has been reported. Patients who desire fertility can be supported. Our research indicates that recurrence rates could be lower in centers where experienced pathologists are making the diagnosis.

Keywords

• Fertility
• leiomyoma
• leiomyosarcoma
• mitotic count
• necrosis
• recurrence

References

1. 1. Mazzei P, Piccolo A, Nugnes L, Mascolo M, De Rosa G, Staibano S. Metabolic profile of intact tissue from uterine leiomyomas using high-resolution magic-angle-spinning ¹H NMR spectroscopy. NMR Biomed. 2010;23(10):1137-1145.
2. 2. De Falco M, Staibano S, Mascolo M, Mignogna C, Improda L, Ciociola F, et al. Leiomyoma pseudocapsule after pre-surgical treatment with gonadotropin-releasing hormone agonists: relationship between clinical features and immunohistochemical changes. Eur J Obstet Gynecol Reprod Biol 2009; 144:44–7.
3. 3. Kurman R, Carcangiu M, Herrington C, Young R. World Health Organisation Classification of Tumors of Female Reproductive Organs, 4th edn. Lyon, France: International Agency for Research on Cancer (IARC) Press; 2014.
4. 4. Gadducci A, Zannoni GF. Uterine smooth muscle tumors of unknown malignant potential: a challenging question. Gynecol Oncol 2019; 154:631–7.
5. 5. Smooth muscle tumour of uncertain malignant potential of the uterine corpus. In WHO Classification of Tumours Editorial Board (Eds.), WHO Classification of Tumours, 5th Edition, Female Genital Tumours, p. 279–280. Lyon: International Agency for Research on Cancer, 2020.
6. 6. Borella F, Cosma S, Ferraioli D, Ray-Coquard I, Chopin N, Meeus P, et al. Correction: Clinical and Histopathological Predictors of Recurrence in Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Multicenter Retrospective Cohort Study of Tertiary Centers. Ann Surg Oncol. 2022;29(13):8319.
7. 7. Kempson RL: Sarcoma and related neoplasms. In: Norris HJ, Heritig AT, Abell MR (eds.). The Uterus. Baltimore: Williams and Wilkins; 1973.
8. 8. Bell SW, Kempson RL, Hendrickson MR. Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol 1994;18 (6):535–58.

9. 9. 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(2):91–112.
10. 10. Kim H-Y. Statistical notes for clinical researchers: assessing normal distribution (2) using skewness and kurtosis. Restor Dent Endod. 2013;38:52–4.
11. 11. Juhasz-Böss I, Gabriel L, Bohle RM, Horn LC, Solomayer EF, Breitbach GP. Uterine Leiomyosarcoma. Oncol Res Treat. 2018;41(11):680-686.
12. 12. Wei JJ. Leiomyoma with nuclear atypia: Rare diseases that present a common diagnostic problem. Semin Diagn Pathol. 2022 May;39(3):187-200.
13. 13. Croce S, Ribeiro A, Brulard C, Noel J-C, Amant F, Stoeckle E, et al. Uterine smooth muscle tumor analysis by comparative genomic hybridization: a useful diagnostic tool in challenging lesions. Mod Pathol 2015;28:1001–10.
14. 14. Chow K-L, Tse K-Y, Cheung C-L, Wong K-W, Cheung ANY, Wong RWC, et al. The mitosis-specific marker phosphohistone-H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome-based study. Histopathology. 2017;70:746–55.
15. 15. Gupta M, Laury AL, Nucci MR, Quade BJ. Predictors of adverse outcome in uterine smooth muscle tumours of uncertain malignant potential (STUMP): a clinicopathological analysis of 22 cases with a proposal for the inclusion of additional histological parameters. Histopathology 2018;73:284–98.
16. 16. Ha HI, Choi MC, Heo JH, Kim KA, Jung SG, Park H, et al. A clinicopathologic review and obstetric outcome of uterine smooth muscle tumor of uncertain malignant potential (STUMP) in a single institution. Eur J Obstet Gynecol Reprod Biol 2018;228:1–5
17. 17. Di Giuseppe J, Grelloni C, Giuliani L, Delli Carpini G, Giannella L, Ciavattini A. Recurrence of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Systematic Review of the Literature. Cancers (Basel). 2022 May 7;14(9):2323.
18. 18. Zheng YY, Liu XB, Mao YY, Lin MH. Smooth muscle tumor of uncertain malignant potential (STUMP): a clinicopathologic analysis of 26 cases. Int J Clin Exp Pathol 2020;13(4):818–26. eCollection 2020.
19. 19. Huo L, Wang D, Wang W, Cao D, Yang J, Wu M, et al. Oncologic and reproductive outcomes of uterine smooth muscle tumor of uncertain malignant potential: a single center retrospective study of 67 cases. Front Oncol 2020;10:647.
20. 20. Zhang C, Gao J, Lu S, Zhang Y, Zhu H. Uterine smooth muscle tumors of uncertain malignant potential (STUMP): A retrospective study in a single center. Eur J Obstet Gynecol Reprod Biol. 2021 Oct;265:74-79.
21. 21. Ciavattini, A; Di Giuseppe, J; Stortoni, P; Montik, N; Giannubilo, S.R; Litta, P, et al. Uterine fibroids: Pathogenesis and interactions with endometrium and endomyometrial junction. Obstet. Gynecol. Int. 2013, 2013, 173184.
22. 22. Shim, J.I; Han, A.K.W; Jeon, H.J; Kim, M.L; Jung, Y.W; Yun, B.S, et al. Clinical experience of uterine smooth muscle tumor of uncertain malignant potential in two gynecological centers: Oncological and obstetrical aspects. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020, 246, 7–13.
23. 23. Yadav, G.; Rao, M.; Goyal, S.B.; Singh, P.; Kathuria, P.; Gothwal, M. Risk of incidental genital tract malignancies at the time of myomectomy and hysterectomy for benign conditions. Obstet. Gynecol. Sci. 2021, 64, 209–215.
24. 24. White MP, Rahimi S, Garely A, Buhl A and Dean RM. Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMP): Review of Pathophysiology, Classification, Diagnosis, Treatment, and Surveillance. J Healthc Commun. 2017, 2:4.
25. 25. Guntupalli SR, Ramirez PT, Anderson ML, Milan MR, Bodurka DC, Malpica A. Uterine smooth muscle tumor of uncertain malignant potential: a retrospective analysis. Gynecol Oncol 2009;113(3):324–6.
26. 26. Vilos GA, Marks J, Ettler HC, Vilos AG, Prefontaine M, Abu-Rafea B. Uterine smooth muscle tumors of uncertain malignant potential: diagnostic challenges and therapeutic dilemmas. Report of 2 cases and review of the literature. J Minim Invasive Gynecol 2012;19:288-95.
27. 27. Travaglino A, Raffone A, Gencarelli A, Caldarelli C, Granata M, Santoro A, et al. Stanford parameters stratify the risk of recurrence in gynecologic smooth muscle tumors of uncertain malignant potential. APMIS. 2021; 129: 283–290.
28. 28. Rizzo A, Ricci AD, Saponara M, DE Leo A, Perrone AM, DE Iaco P, et al. Recurrent uterine smooth-muscle tumors of uncertain malignant potential (STUMP): state of the art. Anticancer Res 2020;40(3):1229–38
29. 29. Dall’Asta A, Gizzo S, Musarò A, Quaranta M, Noventa M, Migliavacca C, et al. Uterine smooth muscle tumors of uncertain malignant potential (STUMP): pathology, follow-up and recurrence. Int J Clin Exp Pathol 7(11): 8136-8142, 2014.
30. 30. Şahin H, Karatas F, Coban G, Özen Ö, Erdem Ö, Onan MA, et al. Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes. J Gynecol Oncol. 2019;30(4):e5
31. 31. 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(7):992–1005.
32. 32. Kalogiannidis I, Stavrakis T, Dagklis T, Petousis S, Nikolaidou C, Venizelos I, et al. A clinicopathological study of atypical leiomyomas: benign variant leiomyoma or smooth-muscle tumor of uncertain malignant potential. Oncol Lett 2016;11:1425-8.
33. 33. Travaglino A, Raffone A, Santoro A, Gencarelli A, Angelico G, Spadola S, et al. Prognostic significance of atypical mitotic figures in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine adnexa. APMIS. 2021; 129: 165–169.
34. 34. Mowers EL, Skinner B, McLean K, Reynolds RK. Effects of morcellation of uterine smooth muscle tumor of uncertain malignant potential and endometrial stromal sarcoma: case series and recommendations for clinical practice. J Minim Invasive Gynecol 2015;22(4):601–6.
35. 35. Peeters N, Hulsbosch S, Ballaux F, Baekelandt J. Uterine smooth muscle tumors of uncertain malignant potential: analysis of diagnoses and therapies illustrated by two case reports. Eur J Gynaecol Oncol 2016;37(3):367–73.