Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMP): A Retrospective Study in A Single Center

Purpose: Uterine smooth muscle tumors of uncertain malignant potential (STUMP) is a heterogeneous group of tumors with histological and biological diversity that cannot be dened as a benign leiomyoma or malignant leiomyosarcoma. The study aims to investigate the diagnostic methods, treatment management and prognosis of STUMP patients in a 13-year period. Methods: We retrospectively reviewed the clinicopathologic information of 31 STUMP patients in Peking University People’s Hospital. Statistical analyses were conducted to compare the difference of clinical characteristics between the women in myomectomy group and those in hysterectomy group. Results: The most common clinical presentation was menstrual disorder. The tumors were mainly manifested as hypoechoic, non-cystic nodules with low blood ow signal by pelvic doppler ultrasonography. Most tumors carried Ki-67 index ranging from 10% to 30%. Immunohistochemical markers such as ER, PR, p16 and Desmin was positively expressed in tumors. At the rst operation, 21 cases underwent myomectomy and 10 cases underwent hysterectomy. The patients in myomectomy group were younger than those in hysterectomy group. In the follow-up period, two cases experienced a relapse in the form of STUMP within 36 months. One case died of cardiovascular accident while the other cases were alive. Six of 21 women in myomectomy group desired pregnancy and two healthy live births were recorded. Conclusion: The diagnosis of STUMP primarily depends on histopathologic features. Fertility-sparing surgery may be a treatment selection for patients with fertility desire. Patients with STUMP, especially in the case of myomectomy, should be informed of recurrence risk and monitored closely.


Introduction
Uterine smooth muscle tumors (SMTs) are categorized as benign leiomyoma (LM) or malignant leiomyosarcoma (LMS) regarding the presence of tumor cytologic atypia, proliferative activity and cell necrosis. Uterine LM is the most frequent benign neoplasm in the reproductive tract of women. LMS is the most common uterine sarcoma accounting for nearly 8% of all uterine malignancies [1], which has greatly contributed to uterine cancer deaths. The diagnosis of uterine SMTs, in most cases, is unequivocal. However, a rare type of uterine SMTs called uterine smooth muscle tumor of uncertain malignant potential (STUMP) shows intermediate phenotypic features and de es easy classi cation. According to the 2014 World Health Organization (WHO) version, uterine independent groups were evaluated using t-test. Categorical variables were assessed using the χ2 test or Fisher's exact test. P-values <0.05 was considered statistically signi cant.

Ethical approval
The institutional ethics committee of Peking University People's Hospital approved this research and a written informed consent was obtained from each case.

Clinical characteristics
We reviewed the medical records of 31 women with STUMP. The women' characteristics are shown in Table 1. The average age of the women was 42.52 ± 11.26 years old. Median gravida was 2 (range 0-4), and median parity was 1 (range 0-2). Of the women, two cases (6.45%) were postmenopausal and 29 cases (93.55%) were premenopausal at the time of diagnosis. Thirteen cases (41.94%) had the symptom of menstrual disorder, and 12 cases (38.71%) had no obvious discomfort. Other less common symptoms are pollakiuria (two cases, 9.68%), abdominal or pelvic mass (two cases, 6.45%) and abdominal distension (one case, 3.22%). Median time of follow-up after surgery was 80 months (range 6-156).

Preoperative evaluation
All women received transvaginal color doppler sonography examination before surgery ( Table 2). The tumor lesion was detected as single in 12 cases (38.71%) and multiple in 19 cases (61.29%). As for tumor echogenicity, two cases (6.45%) were de ned as mixed, and 29 cases (93.55%) as hypoechoic.
Non-cystic tumors (n = 25, 80.65%) were more common than cystic tumors (n = 6, 19.35%). The blood ow signal was detected within or around the tumor in 29 cases. Resistance index (RI) values were < 0.45 in 29.03% women (n = 9), while ≥ 0.45 in 64.52% women (n = 20) . Free uid was detected in only three cases (9.68%). Abdominopelvic computed tomography (CT) was performed in three cases, and two cases were considered to be uterine malignancy. Of the ve cases who had abdominopelvic magnetic resonance imaging (MRI), three cases were suggested with uterine broid degeneration and two cases without abnormal ndings. There were 16 cases with known preoperative serum CA-125 values, and only one case was CA-125 high. The average serum CA-125 value was 19.08 ± 8.77 U/mL.

Pathological ndings
The median tumor size was 7.25 cm (range 2.5-20). 80.65% women (n = 25) had a single STUMP, and 19.35% women (n = 6) more than one STUMP. The anatomical localizations of STUMPs are shown in Table 3. The tumors of 29 cases' were intrauterine (intramural in 23 cases, subserous in two cases and In conclusion, the category and management of STUMP continues to be progressed. The diagnosis for STUMP mainly depends on the histopathological manifestations. No single marker has proved robust enough to incorporate into clinical practice in separating STUMP from other variants, especially for an individual case. However, it would be bene cial to analyze immunohistochemical panel such as PR, ER, Ki-67, p16 and p53. A future perspective may investigate the molecular characteristics of STUMP using the state-of-the-art molecular biology techniques. For women with fertility desire, myomectomy may remain a treatment option. Whether fertility is preserved or not, regular and long-term follow-up through clinical evaluation and imaging examinations is highly recommended for women with STUMP regarding the potential risk of recurrence as LMS.   Abbreviations: HPFs, high-power elds; ER, estrogen receptor; PR, progesterone receptor.