Primary RMS of the uterus is exceedingly rare[1]. and the first case to arise in a postmenopausal woman was documented by Anderson and Ödmansson in 1869. As of now, there have been fewer than 80 reported cases in the English literature. The signs and symptoms of uterine RMS typically include abnormal uterine bleeding(AUB), pelvic pressure/pain, and/or a uterine mass, although some women are asymptomatic[4] .Some studies have reported bleeding accompanied by a foul smelling vaginal discharge as part of the clinical presentation of uterine RMS[5].Our patient was not admitted to the hospital until central nervous system symptoms appeared after venous sinus thrombosis developed. She had almost all of the typical symptoms mentioned above. Unfortunately, all these typical symptoms were ignored. This was partly because she was obese, sexually inexperienced and had irregular periods.
The most common symptom of uterine RMS is AUB which is a common condition, especially in adolescents. A variety of things can cause AUB. Malignant tumors of the uterus comprise a rare cause of AUB. Hence, the presence of AUB in adolescents should be carefully investigated for the possibility of malignant tumors of the uterus so as to avoid delays in diagnosis. In particular, patients with persistent AUB should undergo imaging, pelvic examination and hysteroscopy with biopsy, if indicated. Pelvic ultrasonography is the first line imaging modality for AUB. When ultasonography suspected uterine sarcomas, the chest/abdomen/pelvis by CT or combination MRI/CT should be performed. Following appropriate imaging assessment, the standard approach to diagnosis consists of multiple core needle biopsies or hysteroscopy with biopsy. Confirmation of the type of mesenchymal malignancy by expert pathology review is critical. Our patient did not undergo the process of evaluation and diagnosis of uterine sarcoma mentioned above. During thrombolytic therapy, she developed complete uterine inversion, which was mistaken for a cervical tumor and removed. Finally, postoperative pathology confirmed embryonal RMS of uterus. RMS can be subcategorized histologically and FOXO1 fusion gene status. Histologically, uterine RMSs have been classified into one of the following four types: embryonal, alveolar, spindled and pleomorphic. Embryonal RMS represents the majority of cases and usually affects women of reproductive age. Disease classification of RMS subtypes has been further refined by the identification of fusion-positive RMS and fusion negative RMS. FOXO1(encoding forkhead box protein O1) fusion genes are associated with poor prognosis. In addition to histology and molecular analysis for FOXO1 rearrangement, there are two staging systems to stratify patients with RMS into risk-based therapy groups: the clinical group (CG) and the tumor, node, metastasis (TNM) system. The TNM and CG staging systems complement each other.
To date, uterine RMS is treated with a multidisciplinary approach including surgery, chemotherapy and radiotherapy to improve the cure rate and to prolong the survival time. There is no unified protocol regarding the treatment of uterine RMS associated with inversion, as non-puerperal uterine inversion is an uncommon complication of a malignant uterine mass. It is usually precipitated by tumours exerting traction force on the fundus of the uterus, turning the uterus partially or completely inside out. A review of the English literature revealed that only 6 cases of uterine inversion due to RMS have been reported from 1887 to date, including the present case. Interestingly, the 6 patients ranged in age from 15 to 22 years (mean 18.5 years). All 6 tumors were large, and the average tumor size was 8.8 cm. Regarding the surgical treatment in all cases, a hysterectomy was performed. More details are provided in Table 1. In the literature on uterine inversion, in cases of malignancy, the first surgical maneuver is to return the uterus to its normal anatomic position followed by abdominal hysterectomy.[6] However, this type of surgery described in the literature may not be appropriate for patients such as ours, as the inversed uterus completely prolapsed of the vagina, and thus it was too large to return to its normal anatomic position. Moreover, return the massive inverted uterus secondary to uterine RMS to its normal anatomic position through vagina, which is not a good idea. However, as the enlarged and inversed uterus was removed vaginally, greater difficulties were involved, than would have been encountered with transabdominal hysterectomy. Currently, the data regarding adjuvant therapy for uterine RMS are limited and are usually extrapolated from nonuterine sites. The Intergroup Rhabdomyosarcoma study group compared the various modes of therapy in RMS and concluded that chemotherapy comprising VAC is considered to be the gold-standard treatment option with or without radiotherapy for children and adolescents. While radiotherapy reduces the frequency of recurrence, its impact on 5-year survival has not been proven[7]. An analysis of 171 adult patients with RMS performed by Ferrari et al. revealed treatments similar to those recommended in the pediatric literature produced similar outcomes in the adult population[8]. In adults, however, the same protocols showed much less response[8, 9]. The outcome of uterine RMS is very poor[10]. Our patient experienced rapid spread of neoplastic metastases to the lung and died within 6 months.
Table 1
Author,year | Age(yr) | Histology | presentation | Mass size(cm) | Treatment | Follow-up ststus(mo) |
Case,2005 | 21 | ARMS | Bleeding | 10.2 × 8.2 | NACT, TAH + BSO,CT | ANED(20) |
Ojiwang,2006 | 16 | ERMS | Bleeding | 10.5 × 9.0 | NACT,TAH, RT | |
Sharma,2006 | 18 | RMS | Bleeding vaginal mass | 17 × 15 | TAH + BSO,CT | Pelvic recurrence(12) |
Da Silve,2008 | 15 | ERMS | Bleeding vaginal mass | 11 × 9.7 | TAH,CT,RT | Vaginal recurrence(1.5) DOD(9) |
Ambreen,2019 | 22 | ERMS | Bleeding vaginal mass | 10 × 8 | TAH + BSO, CT,RT | Live metastasis(12) DOD(20) |
Current Case | 19 | ERMS | Venous sinus thrombosis | 18 × 16 | VH + BSO,CT | Pelvic recurrence(2.4) DOD(6) |
ARMS:alveolar RMS; ERMS:embryonal RMS; TAH, total abdominal hysterectomy; BSO: bilateral salpingo-oophorectomy; VH: vaginal hysterectomy; CT: chemotherapy; RT: radiotherapy; NACT: neoadjuvant chemotherapy; ANED indicates alive with no evidence of disease; DOD, dead of disease;. |
Our case illustrates the typical presentation and aggressive behavior of uterine RMS. However, the typical symptoms of uterine RMS were ignored and the diagnosis was delayed. AUB in young women should be a sign to screen for uterine neoplasms. In addition, anatomy should be fully evaluated before proceeding toward surgical intervention to ensure the correct procedure is done.