Pediatr Blood Cancer Risk-Adapted Therapy for Infantile Myoﬁbromatosis in Children Emmanuelle Levine, MD, 1 Paul Fre ´neaux, MD, 2 Gudrun Schleiermacher, MD, 1 Herve ´ Brisse, MD, 3 Ste ´phanie Pannier, MD, 4 Natacha Teissier, MD, 5 Bettina Mesples, MD, 6 and Daniel Orbach, MD 1 * INTRODUCTION Infantile myoﬁbromatosis is a rare disorder deﬁned by prolif- eration of ﬁbroblasts and myoﬁbroblasts. It is one of the most common benign ﬁbrous tumors in infancy [1]. These tumors present as ﬁrm, ﬂesh-colored to purple nodules usually localized in the skin, subcutaneous tissue, muscle, or bone. Three different situations are described: solitary myoﬁbroma, multicentric myoﬁ- broma occurring in soft tissues, and multicentric myoﬁbroma with visceral involvement. This last presentation is associated with high morbidity and mortality despite chemotherapy and surgery due to cardiopulmonary or gastrointestinal complications, while the other forms have an excellent prognosis with surgery alone [1,2]. Most lesions occur before the age of 2 years with a median age of 5 months for multicentric forms and 26 months for solitary forms [3]. Spontaneous regression has been described, probably as a result of massive apoptosis [4]. To improve the knowledge concerning this rare tumor in chil- dren, we present a series of all cases of infantile myoﬁbromatosis treated in our institution over a 9-year period, focusing on a multicentric case, in order to propose treatment guidelines based on this experience and a review of the literature. MATERIALS AND METHODS Data from the ﬁles of all cases of infantile myoﬁbromatosis seen in the Pediatric Department of the Curie Institute, Paris between 2000 and 2009 were retrospectively collected. This de- partment manages about 220 new patients each year for the treat- ment of all solid tumors, excluding leukemias, from birth until adolescence. Case ﬁles were selected from computerized medical records by search software using the item ‘‘myoﬁbromatosis.’’ Various patient data, such as age, gender, clinical, radiologic and histologic characteristics, and treatment details concerning surgery or chemotherapy, were recorded. RESULTS Eight cases presented solitary forms and 1 case presented a multicentric form. The median age of the 9 patients at diagnosis was 10 months (range: 2 days–14 years) with 7 patients under the age of 2 years. The sex ratio was 0.6. Patient characteristics are indicated in Table I. Median follow-up of the cohort was 2.5 years (1–6 years). Solitary Forms The 8 patients with unifocal lesions had no speciﬁc family or personal medical history. Primary tumors involved the head and neck (4 patients pts), limbs (3 patients), or trunk (1 patient; Table I). Various radiologic investigations (X-ray, Doppler US or MRI) were performed in all patients. Fine-needle aspiration, initially performed in 6 patients, showed a benign mesenchymal proliferation with no speciﬁc diagnosis. The deﬁnitive diagnosis was based on biopsy (2 patients) or initial surgery (6 patients). Histologic examination showed that all nodules presented myoﬁ- broblastic characteristics with the presence of interlacing bundles and fascicles of spindle cells with central vascular areas. On immunochemistry, tumor cells presented actin and vimentin staining. Tumor markers such as PS100, desmin, anti-CD1a, and -CD68 were negative in all patients. Positive staining for anti-CD34, a vascular marker, was observed only around vascular endothelial cells. Six patients underwent primary surgical resection with conser- vative tumorectomy. Resection was complete (1 patient) or with a microscopic residue (5 patients). One patient was followed after biopsy only with spontaneous regression of the residual tumor after 24 months of follow-up. One newborn patient with an orbital Background. Infantile myoﬁbromatosis is characterized by proliferation of benign ﬁbrous tumors arising in skin, subcutaneous tissue, muscle, or bone. Solitary and multicentric forms are described. Few reports are available in the pediatric population. Procedure. To improve the knowledge of this rare tumor in infants, the authors present a series of all cases of infantile myoﬁbromatosis treated in their institution over a 9-year period in order to propose treatment guidelines based on their experience and a review of the literature. Results. The authors report a series of 9 cases, 8 solitary forms and 1 multicentric form with visceral involvement treated from 2000 to 2009. Median age was 10 months (range: 2 days– 14 years). Six patients with solitary forms underwent primary surgi- cal resection leading to remission. Only biopsy was performed in 1 case, followed by tumor regression with no recurrence. The last patient with a solitary form was treated by chemotherapy and then surgery allowing remission. The patient with a multicentric form presented complete regression of tumors after 1 year of vinblastine and methotrexate combination chemotherapy. Conclusions. Infan- tile myoﬁbromatosis is a rare soft tissue tumor mainly concerning infants. Surgery is the treatment of choice for solitary forms when excision is possible. Close follow-up may be proposed in the case of inoperable sites. In multicentric life-threatening forms, chemother- apy promotes tumor regression and the vinblastine and methotrex- ate combination is effective with few long-term adverse effects. Pediatr Blood Cancer ß 2011 Wiley Periodicals, Inc. Key words: chemotherapy; fibrous tumor; infantile myofibromatosis; soft tissue tumor 1 Department of Pediatric Oncology, Institut Curie, Paris, France; 2 Department of Pathology, Institut Curie, Paris, France; 3 Department of Radiology, Institut Curie, Paris, France; 4 Department of Pediatric Surgery, Necker-Assistance Publique Hospital, Paris, France; 5 E.N.T. Department, Robert Debre ´-Assistance Publique Hospital, Paris, France; 6 Department of Pediatrics, Louis Mourier Hospital, Colombes, France Conﬂict of interest: Nothing to declare. *Correspondence to: Daniel Orbach, MD, De ´partement de Pe ´diatrie, Institut Curie, 26 Rue d’Ulm, 75005 Paris, France. E-mail: daniel.orbach@curie.net Received 24 June 2011; Accepted 13 September 2011 ß 2011 Wiley Periodicals, Inc. DOI 10.1002/pbc.23387 Published online in Wiley Online Library (wileyonlinelibrary.com).