Results:
An 18-year-old male diagnosed with NF1 (de novo mutation) presented with a 4-month history of abdominal pain and paresthesias in his right lower limb, associating loss of strength and sensory in the last month along with urinary obstruction. Physical examination showed abdominal distension with a palpable mass in addition to numerous subcutaneous neurofibromas, café-au-lait spots, Lisch nodules and axillary ephelides. Abdominal magnetic resonance imaging (MRI) revealed a large retroperitoneal mass with intense heterogeneous contrast enhancement and diffusion restriction as well as innumerable neurofibromas derived from intercostal nerves and lumbosacral plexus (Fig. 1). The suspected diagnosis was a MPNST within a previous neurofibroma. The patient underwent partial surgical resection of the large mass with infiltrated margins. The surgical specimen showed a neoplastic proliferation of spindle cells with marked pleomorphism, frequent mitosis and atypias, forming small fascicles with predominance of perivascular growth. Immunohistochemical staining demonstrated focal positivity for S100, myogenin and desmin, with a proliferative index (Ki 67) of approximately 50%, compatible with high-grade MPNST with rhabdomyoblastic differentiation (Fig. 2). After surgery the patient experience a great improvement of abdominal and lower limb pain as well as urinary obstruction resolution. PET-CT performed three weeks after surgery showed signs of local progression with soft tissue mass enlargement and high FDG uptake (SUV 26.7) together with multiple bilateral pulmonary nodules suggestive of metastasis. Bilateral bone marrow biopsy ruled out tumor infiltration.
The patient started chemotherapy treatment according to European Paediatric Soft Tissue Sarcoma Study Group protocol for rhabdomyosarcoma (EpSSG RMS 2005), based on vincristine (1.5 mg / m2 / day, days +1, +8 and +15), ifosfamide (3000 mg / m2 / day, days +1 and +2), actinomycin (1.5 mg / m2 / day, day +1), and doxorubicin (30 mg / m2 / day, days +1 and +2) in a 21-day interval. The aim of this systemic treatment was to achieve the control of metastatic disease to further consider surgical second-look followed by local radiotherapy. Unfortunately, symptoms progressed after the first cycle and the patient ultimately died of disease progression.
A whole exome sequencing analysis (WES) was performed on surgical material, identifying two genetic gains (duplication/amplification) affecting chromosomal region 7q31.2 of MET gene and 8q24.21 ofMYC gene. Mutational disruption of SUZ12c.1214C>G and TP53 c.681delT were also revealed. No gene fusions were detected. This analysis was only available after the patient passed away and therefore could not be used for therapeutic purposes.