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Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2005
Although rhabdomyosarcoma (RMS) is an uncommon tumor, it is the most prevalent malignant soft-tissue tumor occurring in childhood. Prenatal detection of this tumor, however, is very rare. We describe a possibly unique case of fetal orbital RMS detected in the third trimester of pregnancy by ultrasound examination. The patient was born at 37 weeks and 6 days gestation with a large tumor originating from the left orbit, which showed rapid growth and metastasized within days. After 5 days, she died of sepsis. Histopathological examination revealed a predominantly solid RMS with sparse alveolar elements. This finding is consistent with previous reports suggesting that congenital alveolar RMS is a separate entity with usually a fatal outcome.
A 27-year-old white primigravida woman was referred at 34 weeks, 3 days of gestation because of intrauterine growth retardation and an echo-dense structure in the left orbital region of the fetus. Two earlier scans had not shown abnormalities.
At our obstetrical unit, an ultrasound examination revealed a ball-shaped, protruding tumor covering most of the left side of the fetal face. The tumor consisted of an irregular echogenic mass (Figure 1). It originated from the left orbit and displaced the globe ventrocranially without growing into intracranial structures. Doppler examination showed flow in the tumor. No other major malformations were noted.
Fetal ultrasound at 36 weeks’ gestation shows a tumor originating from the left orbit, measuring 37 × 31 × 48 mm.
The biometry additionally showed a fetus that was small for gestational age, partly explained by placental insufficiency. Both amniotic fluid and fetal movements were normal.
At 36 weeks, the ultrasound examination was repeated and showed an increase of tumor size. Chromosomal analysis revealed a normal 46,XX karyotype and no 13q14 deletion.
Because of the rapid growth of the tumor, a malignancy was suspected. The clinical differential diagnosis included RMS, teratoma, Ewing sarcoma, hemangioma, myoblastoma, and retinoblastoma. After gaining informed consent, we decided to gain neonatal maturity by performing an elective cesarean delivery at 38 completed weeks.
At a gestational age of 37 weeks, 6 days, we performed an emergency cesarean delivery because of late decelerations after the spontaneous rupture of membranes. The newborn with a birth weight of 1720 g (third percentile) had a good start (an Apgar score of 8/9/9 at 1, 5, and 10 minutes). The first examination revealed a large tumor of the left orbit with subtle lobes and a smooth, pink surface. General physical examination revealed no abnormalities and no skin lesions. She was admitted to the neonatal ward for further examination. A magnetic resonance imaging scan showed a large, solid tumor originating from the left orbit, resulting in displacement of the left eye ventrocranially and the nose toward the midline (Figure 2). The tumor grew rapidly and caused diffuse necrosis of the overlying skin (Figure 3). We took a biopsy from the primary tumor at day 3 using a lid crease incision. It revealed a histopathological diagnosis of RMS. On day 4, the neonate showed clinical signs of infection. A sepsis workup was performed and antibiotics were started. She was intubated and ventilated because of respiratory failure. Furthermore, “blueberry-muffin” skin lesions (diameter 5 mm) typical of metastases were detected on the right scapula and in the lumbosacral region. In view of the rapid progressive growth of the tumor and the coexistent small-for-gestational-age condition, curative doses of chemotherapy were considered too toxic and lethal for this child. After 5 days, she died of sepsis.
Magnetic resonance imaging (T2-weighted image) at day 2 shows a large, solid tumor (55 × 55 × 60 mm) originating from the left orbit, displacing the left eye ventrocranially and the nose toward the midline. Bone or cerebral structures are not affected (left, coronal view; right, frontal view).
At day 2, the growth of the tumor had resulted in diffuse necrosis of the overlying skin. Note the displacement of the eye ventrocranially, the nose toward the midline, and the mouth downward.
Postmortem (macroscopic) examination showed a blue-gray, large, solid, lobed tumor, with an ulcerated surface, that was 70 × 75 × 75 mm. The tumor displaced the nose and eye. Multiple metastases were present in the skin, right lung, abdominal wall, liver, and left kidney. We found no cerebral metastases. Microscopic examination revealed an RMS in the primary orbital tumor, the other lesions being metastases.
Histological examination (of the biopsy and postmortem specimens) showed a tumor consisting of slightly cohesive cells with little eosinophilic cytoplasm; round, slightly polymorphic nuclei; and a condensed chromatin pattern. We saw eosinophilic “rhabdoid” inclusions in the cytoplasm. The tumor displayed a solid growth pattern with sporadic alveolar organization. Immunohistochemistry showed positive reaction to smooth-muscle actin, muscle-specific actin, CD56, and skeletal muscle myogenin 4, which is characteristic of RMS (Figure 4 and Figure 5). Reaction to desmine was negative. Cytogenetic analysis revealed no informative translocations.
Histopathology (light microscopy) of the tumor shows a mainly solid tumor of slightly cohesive cells, with sparse but distinct alveolar elements (hematoxylin-eosin, 5-μm section original magnification ×100).
Positive skeletal muscle myogenin 4 staining proves a myogenic origin of the tumor (3,3-diaminobenzidine stain, hematoxylin counterstain, peroxidase reaction, 5-μm section original magnification ×400).
Rhabdomyosarcoma is essentially a disease of childhood, accounting for 4% to 8% of all cancers and for approximately 20% of all malignant soft-tissue tumors in the pediatric population.1 Because RMS is uncommon before 1 year of age and seldom seen in newborns, it is rarely detected by fetal screening. The Intergroup Rhabdomyosarcoma Study2 reported that 0.4% of infants presented with RMS in the first 30 days of life. Only 6 case reports on prenatal detection of RMS have been documented.3-8 Our case is probably the first reported case of prenatally detected orbital rhabdomyosarcoma.
Neonatal RMS is very rare, and when present, it is usually embryonal.2 However, some cases of neonatal alveolar RMS have been reported. Even though in older children, acquired alveolar RMS seems to be associated with a better prognosis than congenital RMS, neonatal alveolar RMS has a very malignant growth pattern. Grundy et al9 reported 10 known cases of neonatal alveolar RMS. Six of the patients had multiple metastatic skin lesions at diagnosis. They also noted that no translocations specific to alveolar RMS could be identified—ie, t(2;13)(q35;q14) and t(1;13)(p36;q14).10 These translocations are detectable in 70% and 10% of cases of nonneonatal alveolar RMS, respectively.
In several cases, treatment has been attempted with different chemotherapy strategies; however, no long-term survivors of neonatal alveolar RMS have been reported.9 Neonatal age implicates several restrictions in therapeutic options: acute toxicity of chemotherapy and radiotherapy can be life-threatening, and the effect on organ systems that have not yet matured can be irreversible. In our patient, the small-for-gestational-age condition and the aggressive nature of the malignancy, together with profound sepsis, precluded attempts at curative chemotherapy.
Correspondence: Dr Schalij-Delfos, Department of Ophthalmology (J3T), Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands (firstname.lastname@example.org).
Financial Disclosure: None.
Acknowledgment: We thank the medical, nursing, and ancillary staff of the Obstetric Department and Neonatal Intensive Care Unit; C. J. Hauptfleisch, MD, PhD, Neonatologist, Department of Pediatrics; F. J. Smiers, MD, PhD, Pediatric Hemato-oncologist, Department of Pediatric Hemato-Oncology; L. Liauw, MD, Radiologist, Department of Radiology; J. E. E. Keunen, MD, PhD, Ophthalmologist, Department of Ophthalmology; and J. V. M. G. Bovee, MD, PhD, Pathologist, Department of Pathology; Leiden University Medical Centre, Leiden, the Netherlands.
Sueters M, Peek AML, Ball LM, et al. Prenatal Detection of Orbital Rhabdomyosarcoma. Arch Ophthalmol. 2005;123(2):276–279. doi:10.1001/archopht.123.2.276
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