Uterine STUMP represents a group of rare, poorly defined borderline tumor in which pathological and clinical features of both LM and LMS overlap. STUMP is found in around 0.01% women who receiving surgery for a presumed diagnosis of uterine LM . Existing literature information for STUMP is limited. Most published reports about STUMP include small sample sizes. Herein, we summarized the clinical characteristics, oncologic and obstetric outcomes of STUMP cases, which provides useful information to the body of knowledge on this disease.
STUMP generally occurs in women of reproductive age. In this study, the average age of STUMP cases was 42.52 years old and the majority of women were premenopausal, which is consistent with previous literatures [5-8]. It is difficult to identify STUMP before surgery and histopathological evaluation. As seen in our cohort of cases, the clinical presentation were stratified as menstrual disorder, pelvic mass or abdominal distension, which are lack of specificity and resemble those of LM and LMS . Imaging modalities are not able to distinguish STUMP from LM and LMS [9,10]. Table 2 indicated that sonographic features with multiple tumors, hypoechoic nodules, high resistance index values, non-cystic appearance and no free fluid were more common in STUMP cases. CA-125 is a valuable biomarker for the diagnosis and prognosis of serous ovarian cancers, whereas it is not a useful indicator for STUMP . We found that serum CA-125 levels in the majority of STUMP cases were in the normal range (Table 2). Therefore, to date no definite imaging techniques and biomarkers are feasible for preoperative diagnosis of STUMP.
The histologic distinction between benign and malignant uterine SMTs remains challenging. In accordance with the literature , our data showed that none were definitely diagnosed as STUMP by the intraoperative frozen section analysis, which may be of limited value in differential diagnosis of such a complex disease in a short time. The pathological diagnosis criteria for STUMP are controversial in some settings. However, all the authors emphasized the three criteria including mitotic index, cytological atypia, and coagulative tumor cell necrosis. The current diagnostic criteria for STUMP may need further refinement. Gupta M et al. proposed that histological parameters, such as atypical mitoses, epithelioid differentiation, infiltrative/irregular margins and vascular intrusion, which raised an alarm for adverse outcomes, should be included in the diagnostic system of STUMP . To aid in the triage of uterine SMTs, immunohistochemical markers including Ki-67, p53, p16 and PR have been employed in reports, in which the profile of STUMP generally defined as being much closer to LM than LMS [13-15]. An obvious increase of Ki-67 proliferation index may be conducive in differential diagnosis of STUMP . Petrović D et al. indicated that Ki-67 expression was negative in all LM and higher than 5% in STUMP and LMS cases . Mutations in the p53 gene, which always participates in the invasion process, is ubiquitous in malignancy. The p16 gene is a tumor suppressor gene involved in the regulation of cell proliferation. The p53 [14-15] and p16 gene  are generally highly expressed in LMS, and has a certain expression in STUMP, but rarely expressed in LM. On the contrary, expression of PR was found in LM and STUMP, but not in LMS . In this study, we found that most cases carried Ki-67 proliferation index ranging from 10% to 30%. More than 80% women had expression of PR, ER and Desmin. About 2/3 cases had p16 positive and 1/3 cases had p53 positive.
Although no standard principles for the management of women with STUMP have been approved, surgery seems to be the primary treatment for STUMP (regardless of surgical approach - abdominal, laparoscopic or hysteroscopic). For STUMP cases who do not desire pregnancy, hysterectomy with or without bilateral salpingo-oophorectomy is considered the gold standard. If fertility preservation is a problem of concern, myomectomy may be a treatment option after balancing the risk of recurrence and fertility preservation. The recurrence rate of is similar for women in myomectomy group and hysterectomy group [6,7,16], and the surgical approach seems to have no influence on the recurrence rate . It is worth emphasizing that morcellation of the tumor is not a good choice because it increased risk of metastasis and relapse suggested by existing evidence [17,18]. In our study, morcellation was used in seven cases of myomectomy group and none of hysterectomy group. The reported recurrence rate for STUMP is 8.7%-11% . Recurrences could be in the form of STUMP or LMS . Our data showed that 6.45% (2/31) cases recurred with the histopathology of STUMP 12-36 months after myomectomy. And one of the two cases who suffered a relapse received morcellation at the first surgery. Some studies explored the relevant factors of recurrence. An interesting finding is that younger women were more likely to recur [16,20]. Sahin H et al. found that the risk of recurrence was higher for subserosal tumors than intramural and submucosal counterparts , while the result from another literature  did not support the conclusion. Statistical analyses indicated that mitosis on pathology was the only independent risk factor for recurrence in the event of STUMP . Expression of immunohistochemical markers such as Ki-67 , p53 [6,20], and p16 [6,20] may be useful in the prediction of the recurrence of STUMP. Recently, Croce S et al. analyzed the genomic profiling by array-comparative genomic hybridization comparing LM, STUMP and LMS cases and proposed that tumors with a genomic index <10 were categorized as nonrecurring STUMPs and those with a genomic index >10 indicated STUMPs with recurrences and unfavorable outcomes . Further, they reported that genomic index with a cut-off = 35 might be a hint for poor overall survival . The treatment choice for recurrence is surgery with or without adjuvant therapy including chemotherapy, radiotherapy and gonadotropin-releasing hormone analogue according to the pathologic type of recurrence. But the truth may be that the therapeutic strategy is mostly determined by the physician’s preferences .
It has been reported that the time to recurrence for STUMP cases ranged from 2 to 194 months , and the five-year overall survival is 92-100% [16,23]. Therefore, a long-term follow-up program deserves to be considered for STUMP cases in spite of favorable prognosis. Especially, close surveillance should be mandatory in the case of myomectomy, and these women should be informed about potential morbidity and mortality of the tumor. No definitive conclusions regarding implementation of follow-up protocols has been achieved. Ip PP et al. suggested that a postoperative evaluation should be conducted every 6 months in the first 5 years and an annual follow-up visit for the next 5 years . Physical examinations and imaging tests including chest radiography, pelvic ultrasound, MRI and/or CT scan are recommended to detect recurrences.