Introduction

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. It is the third most prevalent extracranial solid tumor of childhood after neuroblastoma and Wilms tumor. Almost 50% of all RMSs arise in patients in their first decade of life, and two-thirds of pediatric RMS cases are diagnosed in children under 6 years old. The most common sites for RMS are parameningeal, orbital, head and neck, extremities, and genitourinary system, including bladder, vagina, prostate, and soft tissue around the testicles [1].

RMS has four distinct subtypes: embryonal, alveolar, pleomorphic, and sclerosing/spindle cell. Each subtype has a specific molecular and clinical correlate. In children, there are two major subtypes of RMS – Embryonal rhabdomyosarcoma (ERMS), the most common type which tends to occur in younger children, and Alveolar rhabdomyosarcoma (ARMS), which is more commonly found in adolescents. A third less common variant, the botryoid variety of ERMS, is frequently found in hollow viscera such as the urinary bladder, vagina, and biliary tree. The uterus is one of the least common sites for botryoid rhabdomyosarcoma (BRMS) in the genitourinary tract. Intergroup rhabdomyosarcoma study (IRS) reported that BRMS usually arises from the vagina in infancy and early childhood, whereas uterine localization is more often seen in adolescence. Vaginal bleeding, discharge, or fullness from the mass are commonly seen in BRMS of the vagina or uterus. In children younger than 2 years old, uterine BRMS is rare.

We describe the case of a RMS of the uterus occurred at very young age (under two years of age); since 1959, only 7 cases of uterine botryoid RMS of in infant have been reported.

Patient and Methods

A 15-months-old girl, born at term, with a neonatal weight of 3500 grams, otherwise healthy, with no relevant family history, presented to our Pediatric Emergency Department (ED) for three reddish, smooth, glistening, polypoidal masses protruding from her vaginal introitus (Figure 1). Nine days before arriving at the hospital, her mother noticed a single abnormal mass extruding from the vagina during the diaper change. A gynecologist evaluated the child and clinically detected a vaginal polypoid mass of about 0.5 cm of uncertain interpretation. The labia majora, minora, clitoris, urethra, and perineum appeared normal, and no skin lesion was evident [2].

Differential diagnosis involved all of the polypoid mass protruding from the introitus, ureterocele, vaginal polyps, and hematocolpos.

Within a few days, two other small masses appeared, and the patient returned to the ED. She was in good general conditions. The lesions had a suspicious “grape-like” appearance and tended to come in and out through the vaginal ostium. A pelvic US examination on the patient showed an inhomogeneous aspect of the uterus, which appeared to be occupied and stretched out by an iso-hypoechogenic solid tissue. Additionally, there seemed to be some hyperechogenic spots inside as well as evidence of vascular signals on color doppler (Figure 2).

Tumor markers were dosed (NSE, CEA, Alpha-fetoprotein, CA 19.9, Beta-HCG) and resulted all in range of normality, as urinary catecholamines.

A surgical biopsy revealed a malignant mesenchymal tumor with moderate cellularity. The tumor consisted of oval and spindle-shaped cells arranged without any pattern in a loose myxoid, highly vascular submucosal stroma. An immunohistochemical analysis demonstrated positive anti-desmin antibodies, a weak but diffuse positivity for myogenin, and focal positivity for Myo-D1. The proliferative index was 60%. These findings were consistent with the diagnosis of embryonal rhabdomyosarcoma (ERMS), botryoid type.

Results

The patient was referred to our Pediatric Oncology Group for staging and treatment. The PET-CT scan revealed mild signal enhancement of the uterus with the increased metabolic activity of the vagina. However, the CT scan revealed a total disruption of the uterus and vagina due to the known lesion of 36x45x67 mm with a late central enhancement. No secondary lesions were described. The patient underwent her first cycle of chemotherapy with ifosfamide, vincristine, and dactinomycin (IVA) according to EpSSG RMS2005 protocol, followed by others three cycles one month apart from each other. When she was 18 months old, she underwent a hysterectomy, performed by pediatric surgeons with the supervision of a gynecologist, with the entire mass removed by a Pfannenstiel approach (Figure 3). The postoperative course presented with no complications. Follow-up visits were scheduled quarterly, and at the time of writing the first 12 months were uneventful.

Discussion

RMS is the most common pediatric soft tissue sarcoma and constitutes 4–6% of all malignancies in childhood. Most RMS occurs in the head and neck, followed by the genitourinary tract [1]. The botryoid variant is a type of ERMS arising from embryonic muscle cells and is the most common malignancy in the pediatric female genitourinary tract. ERMS of the vagina usually occurs in early childhood, in contrast with ERMS of the uterus, which occurs later in age [3]. In this case, ERMS of the uterus occurred at a very young age. Since 1959, only seven cases of uterine botryoid ERMS in an infant have been reported.

From the previous reported cases, two of which were cases of recurrent ERMS, the earlier recurrent case was treated with chemotherapy and brachytherapy, while the later one was treated with surgery and chemotherapy, as our case [4]. Patient age varied between seven months and three years.

ERMS is an aggressive form associated with a poor prognosis [5].

Overall, all RMS usually have a worse prognosis with high recurrence rates, ranging from 45–73% (40% recurrence in the lung, 13% in the pelvic area).

Moreover, the majority of patients experiencing recurrence, do so within 2 years after the primary therapy.

Conclusions

Botryoid ERMS of the uterus is a diagnosis not to be missed in an infant. Since rapid diagnosis and treatment are necessary, clinicians should be aware of its presentation to assure optimal management.