Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes

Hanifi Şahin; Funda Karatas; Gonca Coban; Özlem Özen; Özlem Erdem; Mehmet Anıl Onan; Ali Ayhan

doi:10.3802/jgo.2019.30.e54

Journal List > J Gynecol Oncol > v.30(4) > 1125143

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Şahin, Karatas, Coban, Özen, Erdem, Onan, and Ayhan: Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes

Original Article

J Gynecol Oncol 2019;30(4):e54.

Published online: 4 July 2019

DOI: https://doi.org/10.3802/jgo.2019.30.e54

Uterine smooth muscle tumor of uncertain malignant potential: fertility and clinical outcomes

Hanifi Şahin^1,, Funda Karatas², Gonca Coban³, Özlem Özen⁴, Özlem Erdem⁵, Mehmet Anıl Onan², Ali Ayhan⁶

¹Department of Gynecologic Oncology, Malatya Education and Research Hospital, Malatya, Turkey

²Department of Gynecologic Oncology, School of Medicine, Gazi University, Ankara, Turkey

³Department of Obstetrics and Gynecology, School of Medicine, Baskent University, Ankara, Turkey

⁴Department of Pathology, School of Medicine, Baskent University, Ankara, Turkey

⁵Department of Pathology, School of Medicine, Gazi University, Ankara, Turkey

⁶Department of Gynecologic Oncology, School of Medicine, Baskent University, Ankara, Turkey

Correspondence to Hanifi Şahin Department of Gynecologic Oncology, Malatya Education and Research Hospital, Ozalper Mah, Turgut Ozal Bulvarı No. 4/44330, Yesilyurt, Malatya 44090, Turkey. E-mail: hanifi.81_@hotmail.com

Received 31 August 2018 Revised 1 January 2018 Accepted 9 January 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

In this study, we aimed to evaluate the clinicopathological features, obstetric, and oncological outcomes of patients diagnosed with a uterine smooth muscle tumors of uncertain malignant potential (STUMP).

Methods

A dual-institutional, database review was carried out to screen patients with STUMP who were treated with upfront surgery between January 2006 and December 2017. Data including age at the time of diagnosis, recurrence rate, disease-free survival, overall survival, and fertility outcomes were retrospectively analyzed.

Results

Fifty-seven patients with STUMPs were included in the study. The median age at the time of diagnosis was 42 (range, 16 to 75) years. The median follow-up was 57 (range, 16 to 125) months. Eight patients (14%) had recurrence during follow-up. Recurrent STUMPs were seen in seven patients and leiomyosarcoma after 14 months in one patient. Seven patients with a recurrent STUMP survived, while the remaining patient died. Recurrence rates were similar for women who underwent myomectomy and those who underwent hysterectomy. The presence of uterine localization of tumor (subserosal vs intramural-submucosal) statistically significantly affected recurrence rates (odds ratio=5.72; 95% confidence interval=1.349–24.290; p=0.018). Ten of 27 patients who underwent myomectomy for uterine myoma had fertility desire. Seven pregnancies were recorded.

Conclusions

Our study results suggest that fertility-sparing approaches are feasible in patients with STUMP, although recurrence may be seen.

Keywords: Smooth muscle tumors, uterine, Hysterectomy, Recurrence, Myomectomy

References

1. 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.

2. 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; 15:1210–2.

3. Guntupalli SR, Ramirez PT, Anderson ML, Milam MR, Bodurka DC, Malpica A. Uterine smooth muscle tumor of uncertain malignant potential: a retrospective analysis. Gynecol Oncol. 2009; 113:324–6.

4. 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.

5. 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; 22:601–6.

6. 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.

7. Shapiro A, Ferenczy A, Turcotte R, Bruchim I, Gotlieb WH. Uterine smooth-muscle tumor of uncertain malignant potential metastasizing to the humerus as a high-grade leiomyosarcoma. Gynecol Oncol. 2004; 94:818–20.

8. Ng JS, Han A, Chew SH, Low J. A clinicopathologic study of uterine smooth muscle tumours of uncertain malignant potential (STUMP). Ann Acad Med Singapore. 2010; 39:625–8.

9. Croce S, Young RH, Oliva E. Uterine leiomyomas with bizarre nuclei: a clinicopathologic study of 59 cases. Am J Surg Pathol. 2014; 38:1330–9.

10. 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. 2014; 7:8136–42.

11. Croce S, Ribeiro A, Brulard C, Noel JC, 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.

12. Bacanakgil BH, Deveci M, Karabuk E, Soyman Z. Uterine smooth muscle tumor of uncertain malignant potential: clinicopathologic-sonographic characteristics, follow-up and recurrence. World J Oncol. 2017; 8:76–80.

13. Maltese G, Fontanella C, Lepori S, Scaffa C, Fucà G, Bogani G, et al. Atypical uterine smooth muscle tumors: a retrospective evaluation of clinical and pathologic features. Oncology. 2018; 94:1–6.

14. Basaran D, Usubutun A, Salman MC, Narin MA, Boyraz G, Turkmen O, et al. The clinicopathological study of 21 cases with uterine smooth muscle tumors of uncertain malignant potential: centralized review can purify the diagnosis. Int J Gynecol Cancer. 2018; 28:233–40.

15. Soltan MM, Albasry AM, Eldosouky MK, Abdelhamid HS. Immunoexpression of progesterone receptor, epithelial growth factor receptor and galectin-3 in uterine smooth muscle tumors. Cell Mol Biol. 2018; 64:7–12.

16. Conconi D, Chiappa V, Perego P, Redaelli S, Bovo G, Lavitrano M, et al. Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential. Oncol Rep. 2017; 37:41–7.

17. Cao HY, Yang S, Wang S, Deng LY, Lou JY. Is differential expression of p16INK4a based on the classification of uterine smooth muscle tumors associated with a different prognosis? A meta-analysis. Genet Mol Res. 2017; 16:16.

18. Hewedi IH, Radwan NA, Shash LS. Diagnostic value of progesterone receptor and p53 expression in uterine smooth muscle tumors. Diagn Pathol. 2012; 7:1.

19. O'Neill CJ, McBride HA, Connolly LE, McCluggage WG. 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.

20. Atkins KA, Arronte N, Darus CJ, Rice LW. The Use of p16 in enhancing the histologic classification of uterine smooth muscle tumors. Am J Surg Pathol. 2008; 32:98–102.

21. Ünver NU, Acikalin MF, Öner Ü, Ciftci E, Ozalp SS, Colak E. Differential expression of P16 and P21 in benign and malignant uterine smooth muscle tumors. Arch Gynecol Obstet. 2011; 284:483–90.

22. Croce S, Ducoulombier A, Ribeiro A, Lesluyes T, Noel JC, Amant F, et al. Genome profiling is an efficient tool to avoid the STUMP classification of uterine smooth muscle lesions: a comprehensive array-genomic hybridization analysis of 77 tumors. Mod Pathol. 2018; 31:816–28.

23. Dgani R, Piura B, Ben-Baruch G, Open M, Glezerman M, Nass D, et al. Clinical-pathological study of uterine leiomyomas with high mitotic activity. Acta Obstet Gynecol Scand. 1998; 77:74–7.

24. 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.

25. Takeda A, Imoto S, Mori M, Nakamura H. Successful pregnancy outcome after laparoscopic-assisted excision of a bizarre leiomyoma: a case report. J Med Case Reports. 2011; 5:344.

26. Campbell JE, Knudtson JF, Valente PT, Robinson RD, Kost ER. Successful pregnancy following myomectomy for uterine smooth muscle tumor of uncertain malignant potential: a case report and review of the literature. Gynecol Oncol Rep. 2015; 15:1–3.

27. 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.

28. Hughes L, Roex A, Parange A. STUMP, a surprise finding in a large fibroid uterus in a 20-year-old woman. Int J Womens Health. 2018; 10:211–4.

Fig. 1.

A smooth muscle tumors of uncertain malignant potential case with recurrent leiomyosarcoma. A cellular smooth muscle tumor with mild atypia (A) and necrosis of uncertain type (B) (Hematoxylin and eosin stain, ×40).

Fig. 2.

Recurrent tumor as leiomyosarcoma with tumor cell necrosis (A) (H&E ×40) and severe atypia (B) (H&E ×200). H&E, hematoxylin and eosin stain.

Fig. 3.

An atypical smooth muscle tumor containing bizarre cells with hyperchromatic nuclei. Scattered mitotic figures and karyorrhectic nuclei were also seen (hematoxylin and eosin stain, ×200).

Fig. 4.

A smooth muscle tumor with mild atypia (A) and necrosis of infarct-type (B) (hematoxylin and eosin stain, ×100).

Fig. 5.

A cellular smooth muscle tumor (A) (H&E ×100) with brisk mitotic activity (B) (H&E ×400). H&E, hematoxylin and eosin stain.

Table 1.

Demographic and clinicopathological characteristics of patients (n=57)

Characteristics	Values
Age (yr), median	42 (23–69)
Gravida, median	2 (0–6)
Parity, median	2 (0–4)
Tumor size (cm), median	6 (1–26)
Serum CA-125 (U/mL), median	21 (4–65)
>35	10 (17.5%)
<35	28 (49.1%)
Unknown	19 (33.3%)
Smoking habit
Yes	14 (24.6%)
No	39 (68.4%)
Unknown	4 (7%)
Surgical type
TAH	11 (19.3%)
TAH+BSO	14 (24.6%)
TAH+USO	4 (7%)
VH	1 (1.8%)
Abdominal myomectomy	26 (45.6%)
Hysteroscopic myomectomy	1 (1.8%)
Uterine localization
Intramural	38 (66.7%)
Subserous	12 (21.1%)
Submucous	7 (12.3%)
Mitosis
0–5	19 (33.3%)
5–10	32 (56.1%)
≥10	6 (10.5%)
Cellularity
Moderate	11 (19.3%)
High	46 (80.7%)
Necrosis
Absent	48 (84.2%)
Multifocal	9 (15.8%)
Atypia
Mild	14 (24.6%)
Mild to moderate	23 (40.4%)
Moderate	9 (15.8%)
Moderate to severe	11 (19.3%)
Recurrence rate	8 (14%)
After hysterectomy	2 (3.5%)
After myomectomy	6 (10.5%)
Recurrent pathology
STUMP	7 (12.3%)
LMS	1 (1.8%)
Median follow-up (mo), (min-max)	57 (16–125)

LMS, leiomyosarcoma; STUMP, uterine smooth muscle tumors of uncertain malignant potential; TAH+BSO, Total abdominal hysterectomy+bilateral salpingo-oophorectomy; TAH+USO, total abdominal hysterectomy+unilateral salpingo-oophorectomy; TAH, total abdominal hysterectomy; VH, vaginal hysterectomy.

Table 2.

Differences between myomectomy and hysterectomy groups (n=57)

Characteristics	Myomectomy (n=27)	Hysterectomy (n=30)	p-value
Age (yr)	37 (23–52)	46.5 (38–69)	<0.001
Gravida	0 (0–4)	3 (1–6)	<0.001
Parity	0 (0–3)	2 (1–4)	<0.001
Tumor size (cm)	8 (3–25)	5 (1–26)	0.036
Median follow-up (mo)	58 (16–125)	50.5 (20–114)	0.253
Serum CA-125 (U/mL)	22.5 (6–65)	20 (4–60)	0.769
Recurrence rates, No. (%)	6 (22.2%)	2 (6.6%)	0.091

Data shown are median (minimum–maximum) not otherwise specified.

Table 3.

Clinical and pathological characteristics and outcome of patients with recurrence disease (n=8)

Patients	s Age (yr)	Parity	Tumor size (cm)	Initial surgery	Recurrence location	Recurrence treatment	Recurrence pathology	Outcome
1	35	3	16	Myomectomy	Uterus	TAH	STUMP	ANED
2	47	0	5	Myomectomy	Uterus	TAH+BSO	STUMP	ANED
3	38	0	9	Myomectomy	Uterus	Myomectomy	STUMP	ANED
4	45	2	13	TAH+BSO	Pelvic RP mass	Mass excision	STUMP	ANED
5	35	0	2	Hysteroscopic myomectomy	Uterus	Hysteroscopic myomectomy	STUMP	ANED
6	52	0	20	Myomectomy	Pelvic+ upper abdominal mass	Debulking+ chemotherapy	LMS	DOD
7	30	1	4	Myomectomy	Uterus	TAH	STUMP	ANED
8	39	2	11	TAH+USO	Pelvic RP mass	Mass excision	STUMP	ANED

STUMP, uterine smooth muscle tumors of uncertain malignant potential; TAH+BSO, total abdominal hysterectomy+bilateral salpingo-oophorectomy; TAH+USO, total abdominal hysterectomy+unilateral salpingo-oophorectomy; ANED, alive with no evidence of disease; RP, retroperitoneal; CT, chemotherapy; DOD, dead of disease; LMS, leiomyosarcoma.

Table 4.

Differences between non-recurrence and recurrence groups (n=57)

Characteristics	Non-recurrence group (n=49)	Recurrence group (n=8)	p-value
Age (yr), median	42 (23–69)	38.5 (30–52)	0.418
Gravida, median	2 (0–4)	1 (0–4)	0.228
Parity, median	2 (0–3)	0.5 (0–3)	0.159
Tumor size (cm), median	6 (1–26)	10 (3–20)	0.160
Median follow-up (mo)	56 (25–114)	64 (16–125)	0.512
Serum CA-125 (U/mL), median	20 (4–60)	28 (17–65)	0.167
Smoking, No. (%)	12 (24.5%)	3 (37.5%)	0.531
Type of surgery, No. (%)			0.353
TAH	11 (22.4%)	0
TAH+BSO	13 (26.5%)	1 (12.5%)
TAH+USO	3 (6.1%)	1 (12.5%)
VH	1 (2%)	0
Myomectomy	21 (42.9%)	6 (75%)
Uterine localization, No. (%)			0.002
Intramural	37 (75.5%)	1 (12.5%)
Subserous	7 (14.3%)	5 (62.5%)
Submucous	5 (10.2%)	2 (25%)
Mitosis, No. (%)			0.399
0–5	18 (36.7%)	1 (12.5%)
5–10	26 (53.1%)	6 (75%)
≥10	5 (10.2%)	1 (12.5%)
Cellularity			0.659
Moderate	9 (18.4%)	2 (25%)
High	40 (81.6%)	6 (75%)
Atypia			0.379
Mild	11 (22.4%)	3 (37.5%)
Mild to moderate	22 (44.9%)	1 (12.5%)
Moderate	7 (14.3%)	2 (25%)
Moderate to severe	9 (18.4%)	2 (25%)
Necrosis			0.783
Absent	41 (84.2%)	7 (87.5%)
Multifocal	8 (15.8%)	1 (12.5%)

TAH+BSO, total abdominal hysterectomy+bilateral salpingo-oophorectomy; TAH+USO, total abdominal hysterectomy+unilateral salpingo-oophorectomy; TAH, total abdominal hysterectomy; VH, vaginal hysterectomy; STUMP, uterine smooth muscle tumors of uncertain malignant potential.

Table 5.

Univariate analysis of recurrence risk factors

Variables	p-value	Univariate analysis
Variables	p-value	OR	95% CI
Age (yr)	0.432	0.56	0.133–2.367
<42
≥42
Parity	0.184	0.37	0.089–1.591
<2
≥2
Tumor size (cm)	0.501	0.60	0.139–2.621
<6
≥6
Smoking	0.818	0.83	0.180–3.883
Yes
No
Surgical type	0.157	0.31	0.063–1.563
Hysterectomy
Myomectomy
Uterine localization	0.018	5.72	1.349–24.290
Intramural-submucous
Subserous
Necrosis	0.784	0.73	0.079–6.795
Absent
Multifocal
Cellularity	0.661	0.67	0.117–3.908
Moderate
High
Mitosis	0.446	0.24	0.027–2.174
0–5
5–10
≥10
Necrosis	0.784	0.73	0.079–6.795
Absent
Multifocal
Atypia	0.468	0.81	0.111–5.987
Mild
Mild to moderate
Moderate
Moderate to severe

Table 6.

Clinical and pathological characteristics of patients with obstetrics outcomes (n=7)

Patient	Age (yr)	Gestational age (wk)	Parity	Tumor siz (cm)	e Initial surgery	Recurrence location	Recurrence treatment	Recurrence pathology	Birth type	Fertility outcome
1	35	38	3	16	Myomectomy	Uterus	TAH	STUMP	C/S	2,800 g, live birth
2	36	35	0	5	Myomectomy	–	–	–	C/S	2,200 g, live birth
3	25	39	0	6	Myomectomy	–	–	–	C/S	3,450 g, live birth
4	23	39	0	8	Myomectomy	–	–	–	C/S	3,150 g, live birth
5	26	39	1	10	Myomectomy	–	–	–	C/S	3,600 g, live birth
6	38	38	0	11	Myomectomy	–	–	–	C/S	3,100 g, live birth
7	30	38	1	3	Hysteroscopic	Uterus	TAH	STUMP	VB	3,200 g, live birth
					Myomectomy

STUMP, uterine smooth muscle tumors of uncertain malignant potential; TAH, total abdominal hysterectomy; VB, vaginal birth; C/S, cesarean section.

TOOLS

Similar articles