Primary Peritoneal Rhabdomyosarcomatosis in a 2-Year-Old Child Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy — Case Report and Review of Literature

Abstract

Pediatric peritoneal sarcomatosis is an exceedingly rare entity with unknown incidence. Within these tumors, primary peritoneal rhabdomyosarcoma constitutes a small fraction. Majority of them are probably treated inadequately and have dismal outcomes. A favorable subset exists where aggressive treatment in the form of cytoreductive surgery supplemented by hyperthermic intraperitoneal chemotherapy in the multimodal setting can be attempted. We present a case of primary peritoneal embryonal rhabdomyosarcoma in a 2-year-old child who was treated with systemic chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy while avoiding radiation, with its evidence and rationale.

Introduction

Rhabdomyosarcoma (RMS) is the third most common extra-cranial malignancy of childhood [1]. The abdomen itself is a rare location seen in 10–12% of patients [2]. Primary peritoneal RMS is an extremely unusual entity and in a combined Italian and German study group; none of the 161 abdominal RMS patients had primary peritoneal RMS [2]. Peritoneal sarcomatosis has a poor prognosis and is the most often treated with palliative chemotherapy or radiation with understandably dismal results. As experience with multimodal management of Desmoplastic small round cell tumor (DSRCT) with aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has grown, other pediatric peritoneal malignancies are also being viewed with potential curative intent. The evidence for CRS-HIPEC in RMS is largely extrapolatory from other pediatric sarcomas and, in properly selected patients, concedes favorable results.

Case Report

A 2-year-old male child was brought to our clinic with a 10-day history of an abdominal lump. An 8-cm firm pelvic mass was palpable reaching the umbilicus. A contrast-enhanced computerized tomography (CECT) of the abdomen showed a 10-cm heterogeneous mass with necrotic components arising from the rectovesical pouch with ascites and peritoneal deposits over both subdiaphragmatic areas. Biopsy of the pelvic mass confirmed RMS based on immunohistochemical positivity of tumor cells for desmin and negative for synaptophysin, pan cytokeratin (AE1/AE3), and leukocyte common antigen (LCA). The tumor cells retained INI1, and translocation studies for PAX3 and PAX7 fusions with FKHR were negative. Fluorodeoxyglucose (FDG) avidity with a maximum standardized uptake value (SUVmax) of 59.8 was noted in the pelvic mass (Fig. 1A) with lower activity in the peritoneal deposits on FDG positron emission tomography (PET) scan. There were no other sites of significant FDG uptake (Fig. 1B). Bone marrow evaluation was negative for metastasis. A final diagnosis of primary peritoneal embryonal RMS was made.

Fig. 1.

A Prechemotherapy PET scan demonstrating large mass with FDG avidity and necrotic non FDG avid components. B Prechemotherapy PET scan showing ascites and right and left subdiaphragmatic FDG avid peritoneal deposits (white arrows). C Response PET CECT showing complete metabolic response with reduction in size of pelvic mass (white arrow). D Response PET indicating complete disappearance of ascites and peritoneal deposits

Patient was started on induction chemotherapy with vincristine, dactinomycin, and cyclophosphamide. Response assessment was done with PET CECT that showed reduction in the size of the primary lesion to 3.3 cm (Fig. 1C) without significant FDG activity in either the pelvic mass or the peritoneal deposits and complete resolution of ascites (Fig. 1D). After discussion in the multidisciplinary clinic, patient was planned for CRS and HIPEC if complete cytoreduction was achievable.

With a midline laparotomy, disease assessment was done, and peritoneal carcinomatosis index (PCI) [3] was calculated to be 8 with disease localized to pelvis, right and left anterior parietal peritoneum, right and left subdiaphragmatic peritoneum, and nodule at the base of falciform ligament and right paracolic peritoneum (Fig. 2A). The pelvic mass was arising from the peritoneal reflection over the bladder without infiltration of the bladder wall and was adherent to the left internal iliac artery, which was sacrificed. There were enlarged left external iliac nodes adherent to the mass. Fixed retractor system was mounted after bilateral anterior parietal peritonectomy. Visceral sparing pelvic peritonectomy, stripping of the peritoneum covering both hemi-diaphragms, peritonectomy of the hepatorenal pouch, and right paracolic peritoneum and en bloc excision of the falciform ligament until its entry into the umbilical fissure were performed by dividing the bridge of liver tissue connecting segment 4b and segment 3 (Fig. 2B, C, D). Bilateral pelvic node dissection and complete omentectomy were also performed. Silk stitches were taken at wound edges, which were suspended onto the fixed retractor system to increase the volume of the peritoneal cavity (Fig. 3A). Absolute hemostasis was achieved prior to initiation of HIPEC. Using cisplatin at 100 mg/m² for 90 min at 41.5–42 °C via the open–coliseum technique, HIPEC was delivered while maintaining systemic normothermia. Single inflow and outflow tubings with temperature probes were used (Fig. 3B), and chemotherapy was diluted in 1.5% isotonic peritoneal dialysis fluid (Fig. 3C). Duration of the entire procedure was 220 min with a blood loss of 100 ml. Intraoperative and postoperative course was uneventful, and the patient was discharged on the 6th postoperative day. There were no re-admissions for surgery-related complications.

Fig. 2.

A Large deposits in the rectovesical pouch (arrow) and bladder peritoneum (arrow head). B Completed right diaphragmatic peritoneal stripping (single arrow), peritonectomy of hepatorenal pouch (arrow head), and right paracolic peritonectomy (double arrows). C Completed visceral sparing pelvic peritonectomy with bilateral pelvic node dissection. D Specimen of right parietal peritonectomy. Falciform ligament with nodule at base (white arrow), right diaphragmatic peritoneum with nodules (arrow head), right paracolic peritoneum (black arrow), and pelvic peritonectomy (double arrows)

Fig. 3.

A Wound edges suspended by stitches to the fixed retractor system. B Inflow and outflow tubes in place. C Ongoing HIPEC with cisplatin in peritoneal dialysate carrier

Histopathology revealed 30% viable RMS in the pelvic mass with multiple small deposits of residual RMS in the pelvic, paracolic peritoneum, and omentectomy specimen. In addition, two nodes in the left external iliac group had metastasis. There was no histologic involvement of the internal iliac artery. The patient completed the maintenance chemotherapy without delays. Radiotherapy (RT) was avoided as local therapy was augmented by HIPEC. At the time of drafting the manuscript, the child was disease free for 10 months.

Discussion

Peritoneal sarcomatosis in children is very rare with only few cases in literature. The exact incidence of this entity remains unknown. The histologies in peritoneal sarcomas are usually DSRCT, RMS, gastro-intestinal stromal tumors, and liposarcoma. Except for RMS, the other histologies are diseases of older children and adolescents. Peritoneal disease from RMS can occur secondary to tumor dissemination from a known abdominal or retroperitoneal primary site, either spontaneously or by tumor manipulation. Even more infrequent is primary peritoneal RMS, when no other primary site is discernable.

In the largest series until date of pediatric peritoneal disease, Hayes-Jordan et al. reported 50 cases of which RMS accounted for 7 of them [4]. Whether these children had primary peritoneal disease or secondary dissemination is not mentioned. Zmora et al. recently published a series of 9 pediatric patients with peritoneal disease [5]. RMS accounted for 3 of them, and only 1 patient had primary peritoneal RMS and the other two had either a retroperitoneal primary or recurrent metastatic disease. In a series by Casey et al., of the 10 patients with abdominal sarcomatosis, only 1 had primary peritoneal RMS [6]. In addition to these, there is one case report of peritoneal RMS by Kawamura et al. [7].

Among the subtypes of RMS, embryonal variety has a more favorable prognosis and is often seen in younger pediatric patients. Within the reported cases of primary peritoneal RMS, we report the youngest patient to be treated with complete CRS and HIPEC.

Majority of evidence for HIPEC comes from prospective and retrospective cohort studies from MD Anderson Cancer Center, and even in their series, RMS constituted a minority (7 of 50 cases) and the majority was DSRCT. They demonstrated that patients with PCI < 16 had a median disease-free survival (DFS) for 34 months as opposed to 20 months for PCI >16 [4]. Similarly, macroscopic residue <2.5 m had a DFS of 31.4 months versus 7.1 months with larger residual disease. In addition, presence of extra-abdominal disease and non-DSRCT histology had poorer DFS without significant difference in overall survival (OS). In a phase II prospective cohort study, 79% 3-year OS was demonstrated after complete CRS and HIPEC in 20 children with abdominal sarcomatosis; however, only 2 patients had RMS [8]. HIPEC in all of the above series for RMS was with Cisplatin at 100 mg/m² for 90 min. The safety of this dosing was studied in a phase I study where the dose-limiting side effect was renal toxicity [9]. Grade III renal toxicity was seen in 18%, and 1 patients (3.7%) required temporary dialysis. Overall HIPEC with cisplatin was considered reasonably tolerable. Similar drug, dosing, and duration was used in our patient.

The pediatric surgical oncology unit of the author has performed CRS and peritonectomy without HIPEC for pediatric germ cell tumors and abdominal RMS prior to this report. HIPEC is routinely performed in adult patients at our institution, and this was the first case of HIPEC in a toddler. Unlike the closed technique used at MD Anderson, we are comfortable with the open method for HIPEC [4]. The evidence for HIPEC for peritoneal sarcomatosis is growing, and safe techniques from adult surgery are reproducible in pediatric patients as well. This allows curative intent treatment to be delivered without disproportionately increasing toxicity.

Peritoneal dissemination is considered stage IV and usually treated as high-risk disease. However, it can be argued that peritoneum is a single organ, and in the absence of visceral or extra-abdominal metastasis, they can be considered loco-regional disease, more so when the primary site is the peritoneum. Especially in the case of embryonal RMS if complete loco-regional clearance is achieved, patients can be stratified as non-high-risk. Conventionally, adjuvant whole abdominopelvic radiation therapy (WAP-RT) is recommended, but the evidence comes from children with incomplete or no CRS and without HIPEC. WAP-RT is fraught with adverse events especially in pediatric patients due to large fields. Casey reported 10 patients with abdominal sarcomatosis treated with incomplete cytoreduction and WAP-RT [6]; 40% developed acute grade 4 hematologic toxicity. Long-term effects, even with intensity modulated RT techniques, include transfusion dependency, growth retardation, and vertebral and pelvic deformities [10]. Since our patient underwent complete CRS and local control was augmented with HIPEC, we decided to avoid WAP-RT based on multidisciplinary discussion. Our decision was also influenced by embryonal histology; good response to chemotherapy, absence of extra-abdominal disease, and the very young age of the child with the intent to avoid radiation related long-term morbidity. These favorable features along with low PCI and the achievement of complete cytoreduction at surgery will allow a predicted DFS of over 3 years in our patient in accordance with available data [4, 8]. The question of cure cannot be answered at present and longer follow-up will be required.

There is unlikely to ever be level I evidence for such rare diseases, and treatment consensus will have to be derived from prospective and retrospective reviews of case series and isolated case reports. When complete cytoreduction is possible, aggressive surgery and possibly HIPEC should be pursued in a multimodal setting with the opportunity of cure in select patients. Such children should be referred to high-volume centers where there is expertise for peritonectomy, HIPEC, and critical care services that are familiar with the management of HIPEC patients. Before embarking on major therapeutic endeavors for advanced diseases, multidisciplinary discussions should concur on the treatment plan with extensive counseling of the family regarding realistic expectation of outcomes.

Conclusion

Primary peritoneal RMS is an extremely rare disease constituting a very small fraction of pediatric sarcomatosis. Majority of them are treated with palliative chemotherapy, incomplete surgery or RT. A select subset of these tumors may have favorable outcomes, and aggressive surgery to achieve complete cytoreduction followed by HIPEC in a multimodal setting should be offered with a possible curative intent. Evidence for HIPEC after complete cytoreduction in pediatric sarcomatosis is growing and should be performed for diseases without unfavorable characteristics. Safety of these complex procedures can be ensured by referral to centers with a team experienced in the techniques and their postoperative care.

Abbreviations

CECT

Contrast-enhanced computerized tomography

CRS

Cytoreductive surgery

DFS

Disease-free survival

DSRCT

Desmoplastic small round cell tumor

FDG

18 Fluorodeoxyglucose

HIPEC

Hyperthermic intraperitoneal chemotherapy

OS

Overall survival

PCI

Peritoneal carcinomatosis index

PET

Positron emission tomography

RMS

Rhabdomyosarcoma

SUVmax

Maximum standardized uptake value

WAP-RT

Whole abdominopelvic radiation therapy

Author Contribution

Mufaddal Kazi: Designed and wrote the manuscript; performed surgery

Sajid S. Qureshi: Designed and critically reviewed the manuscript; performed surgery

Data Availability

All data was retrieved from electronic medical records of the hospital.

Declarations

All procedures followed were in accordance with the ethical standards of the responsible committee (institutional and national). Ethics committee approval was not required for the case report. Consent for publication from the patient was obtained.

Competing Interests

The authors declare no competing interests.