Recurrent metastases in malignant tumor of left forearm
Short Summary

4-year-old boy presented with a lesion on his left forearm was diagnosed with small cell malignant neoplasm. It was thought that he had a malignant myoepithelioma but other reports suggested a primitive poorly differentiated neoplasia of neuro-ectodermal origin. He underwent surgery and chemotherapy but subsequently developed pulmonary metastases. The treating doctors recommended a second line chemo approach.

Patient's Questions

1) Suggested therapy?
2) What is the prognosis?

Medical Background

A 4 year old male was diagnosed with malignant neoplasia of left forearm. Following the appearance of a palpable tumefaction on the ventral surface of the left forearm, an echotomography was carried which showed a neoformation having a non-specific diagnostic interpretation. 

The Patient was examined as an outpatient and a decision was made to carry out further diagnostic tests, as follows:
- Needle aspiration: results suggested a small-cell malignant neoplasia;
- MRI of left arm: showed a solid neoformation measuring 5 x 2.4 x 1.8 cm, not clearly differentiated from the radial artery and involving the radial nerve;
- Stadiation CAT scan of chest and abdomen, negative in terms of repetitive lesions in the organs that were examined.
Given the results of these tests, a decision was made to limit the initial surgical approach to a biopsy and to carry out chemotherapy before proceeding with excision of the neoplasia.
The patient had a lymphoscintigraphy to find the sentinel lymph node in the left axilla.  The patient had a surgery under general anesthesia to take a biopsy of the mass on his forearm and the radio-marked axillary lymph node was resected.
Initial assessment of biopsy sample confirmed the suspected malignant lesion and positive axillary sentinel lymph node, a central venous catheter was inserted percutaneously in the right internal jugular vein and bone and marrow biopsies were taken.
The patient had 4 cycles of chemotherapy with Epirubicin, CDDP and 5-FU c.i.
Follow-up MRI showed fairly good response to treatment, and 3 more cycles of chemotherapy were given in accordance with the VAIA regimen (vincristine, actinomycin-D and ifosfamide). During his last hospitalization for chemotherapy the dimensions of the hard neoformation were 6 x 4.8 x 3.5 cm compared with those at diagnosis of 5.5 x 9 cm.
Given the reduction in size of the tumor the patient had surgery to remove the neoformation which surrounded the radial nerve. The surgical procedure allowed the two terminal branches of the radial nerve to be isolated (superficial sensory branch and deep motor branch) and the latter one saved. The sensory branch was reconstructed using autologous implantation of both sural nerves.  The resection of the neoplasia was conservative in terms of muscular function, since  the long and short supinator muscles were only partially compromised.
Histology diagnosis was neoplasia with small elements having a prominent nucleus and arranged in solid nested groups or gland-like on a mixoid background. Immunohistochemistry showed neuroectodermic differentiation (Syn-positive in occasional cells, CD56+, S100+ in some cells) and occasionally positive for cytokeratins.  The overall condition indicates a primitive neuroectodermic neoplasia.
In addition, a perisurgical interstitial HDR brachytherapy was administered dose in 12 Fractions (2 fractions a day with an interval of 6 hours) and was prescribed at isodose of 90%, at 0.5 cm from the axis of the vectors. 
Chest CAT scan showed distributed multiple secondary lesions, dimensions of from a few millimeters to a couple of centimeters.  The largest of these was observed in the right posterior inferior para-hilar region, with maximum size of about 2 cm, and was dishomogeneously hypodense centrally. The anterior mediastinum had extensive hypodense tissue, likely related to the thymus.

Expert's Opinion

Patient's History
Medical Diagnosis: Malignant neoplasia of left forearm
The patient has recurrent metastatic solid tumor with unclear etiology. Initial pathology report suggested a myoepithelioma. Subsequent pathology reports suggest a sarcomatous etiology. The patient was given multiple chemotherapeutic agents and agents that would be theoretically active against either tumor. He had only a poor tumor response, but also subsequently developed presumptive pulmonary metastases. 
A patient with recurrent, refractory and metastatic disease has a poor prognosis. Chance of long term survival is less than 20%. Multiple phase 1 or 2 studies using a variety of chemo based regimens include regimens of navelbine, topotecan, Gleevac, depsipetide, Tarceva and pemetrexad. Unfortunately, many of these agents are available only on protocol. In addition, many are unproven, with theoretical but not demonstrated efficacy.
Given the current situation, there are two approaches that should be considered. Solid tumors in pediatrics have been shown to be effectively treated on occasion by second line regimens. The use of topotecan/ carboplatin seems reasonable. If there is a response, cytoxan VP-16 also seems reasonable.  An alternative may be the use of autologous stem cell transplantation. It appears that the patient has no bone marrow metastases; conceivably, he could undergo an autologous harvest. He could receive high dose cytotoxic chemotherapy, followed by stem cell rescue. In this way he could have an intensification of therapy (the CCG protocol used melphalan and total body irradiation).
It is unfortunate that most of the information in the literature suggests that this is a difficult problem. Most of the above solutions are difficult and, for the most part, unproven.   However, I am not sure that a simple solution is available, and I would defer to the primary care givers regarding the above suggestions.