Pediatric Rhabdomyosarcoma (RMS) of The Genitourinary Tract

What is Pediatric Rhabdomyosarcoma (RMS) of the genitourinary tract?

It can arise from bladder and prostate. From para-testicular, vaginal/uterine/vulvar regions. It is a tumor that arises from the skeletal muscle and can be present at any part of the body. Most common locations are non-genitourinary regions. In genetic RMS, paratestis is the most common area affected. Other areas could be bladder, testis etc. It is the most common soft tissue sarcoma in infants and children.

RMS is derived from the embryonic mesenchymal tissue, specifically striated muscles. These tumors arise from multiple locations, including head and neck extremities and the genito urinary tract. It is one of the “small round blue cell tumors” of childhood (Ewing's sarcoma, Medulloblastoma, Neuroblastoma, and Wilms comprise other tumors.) microscopically resembles fetal skeletal muscle cells. 20-25% cases arise from GU sites, prostate, bladder, paratesticular, vagina and uterus.

Epidemiology

There is a bimodal age distribution with a peak incidence in the first 2 years and again in adolescence. The incidence of RMS in the US is 4.5 cases per million children adolescents per year. A slight male predominance is seen, with a ratio of 1.37 (incidence 5.2 bs 3.8/1,000,000).

Histology

Embryonal RMS is the most common subtype – includes sarcoma botryoides, a polypoid variety that occurs in the bladder or vagina. Alveolar RMS is the second most common form and has a worse prognosis and higher rate of local recurrence.

Risk Factors

The majority of the RMS cases are sporadic. A small portion is associated with a genetic disorder Li-Fraumeni Syndrome, and Neurofibrometasis Type I.· The risk factors include:

• Advanced maternal age (>35 years).
• High birth weight (>4000gm)
• Large for gestational age.
• Maternal drug use.
• In utero exposure to radiation.

Prognostic Factors

Staging is the most predictive outcome. Unfavorable prognostic factors are as follows:

• Alveolar history
• Unfavorable sites. (Bladder and prostate)
• Presence of distant metastatic sites.
• Involved regional lymph nodes.
• Primary tumors greater than 5cm.
• Age less than 1 or greater than 10 years.
• PAX/FOXO1 fusion (translocation of chromosome 1;13or 2;13).

Fusion Status in RMS

Approximately 80% of the RMS cases show a chromosomal translocation between either PAX3 (Chr 2), or PAX7 (Chr 1) and FOXO1 (Chr 13). The presence of a subsequent gene fusion is a useful prognosis marker and refers to an inferior event-free and overall survival compared to fusion negative cases. The remaining 20% of the alveolar RMS are fusion gene negative and behave similar to ERMS.

Primary Location and Presentations

Bladder tumors grow within the lumen. Prostate often becomes large and the pelvic mass spreads early. Bladder and prostate RMS typically present with hematuria, urinary retention, and constipation. Vaginal tumors are commonly Botryoid. Para-testicular tumors usually present as painless tumors. Testis can drain to the retroperitoneal lymph nodes.

Treatment

• Para testicular – High inguinal Radical Orchiectomy.
• Bone marrow biopsy and aspirate.
• If >10 years of retroperitoneal mets in CT scan. Ipsilateral Template Retroperitoneal Lymph Node Dissection (RPLND).
• Adjuvant chemotherapy.
• Radiation should be given in the presence of metastasis.

Pelvic primary = Bladder/ Prostate/Vagina

• Initial multimodal approach biopsy, Mediport, BM biopsy, Chemotherapy.
• Upfront radical surgery is rarely advised.
• After initial biopsy and staging appropriate chemotherapy.
• Then reassess decision for local control the approaches could be
• Radiation +/- Surgery.
• May require cystectomy, hysterectomy etc.
• May require urinary reconstruction.

Radiotherapy

Radiation dosage and timing depends upon staging, risk and histology, anatomic location of the tumor. It has been shown to be very effective for local tumors as local recurrence is most common so radiation helps to prevent this. Typically, children with embryological history who underwent complete surgical resection do not receive radiation, while those with completely resected alveolar histology (group I, intermediate-risk) do. COG currently recommends that all patients with group II-IV receive radiotherapy along with selected group I patients.

Prognosis 

• Paratesticular
  • Stage I embryological – 95% Overall Survival.
  • Stage I Alveolar – 90% Overall Survival.
  • Stage IV – 25% Overall Survival.
• Vaginal / Uterine
  • Overall Survival 82% (94% in those <10 years, 76% in >10 years)
• Bladder/ Prostate
  • Non metastatic
  • Embryonal 83% (Botryoid 92%) Overall Survival.
  • Alveolar: 40% overall survival, so poor prognosis.
  • In metastatic cases the Overall Survival is 10-20%.
• So from here it can be postulated that paratesticular and vaginal and uterine the prognosis is better. In bladder and prostate it is a bad prognosis.

Hope you found this blog helpful for your NEET SS Surgery Urology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.