Malignant extrarenal rhabdoid tumor: a case report

Introduction

Fetal malignancies of the upper or lower extremities are rare and hard to detect or classify in utero. There are several differential diagnoses that should be considered, including lymphangioma, hemangioma, teratoma, and rhabdomyosarcoma. Because of different prognoses of these tumor entities, a postnatal progression of the disease is often hard to estimate.

We describe the extremely rare case and individual perinatal management of a rapidly growing fetal extrarenal rhabdoid tumor.

Presentation of the case

A 35-year-old gravida 2 para 1 was sent to our department of perinatal medicine at 31+2 weeks of gestation because of a newly diagnosed mass in the right fetal upper arm. The mother was obese (BMI 42.9 kg/m²) and had a history of primary cesarean section. Gestational diabetes had been diagnosed and dietetically well adjusted. Differentiated fetal ultrasound showed polyhydramnios (single deepest pocket was 11 cm), fetal macrosomia (>95^th percentile of normal growth) and an enormous enlargement of the right upper arm. While the humerus was measured at normal length, the circumference of the upper arm was 22.5 cm (Figure 1). The soft tissue was of homogenously increased echogenicity, color Doppler could not reveal hypervascularization with any certainty. There were no signs of associated anomalies. After having been counseled by obstetricians and neonatologists, the parents opted for a conservative approach because of advanced pregnancy. Ultrasound control at 32 weeks of gestation showed increasing diameter of the right upper arm from 7.3 cm to 8.6 cm (Figure 2). At 33+1 weeks of gestation, the mother presented with regular contractions. Amniotic fluid index was 29 cm. As serum analysis and the patient’s symptoms pointed to preeclampsia (aspartate aminotransferase 41.0 U/L, alanine aminotransferase 51.0 U/L, blood pressure >140/90 mmHg, proteinuria) fetal lung maturity was initiated by application of 12 mg betamethason once. However, as fetal heart rate monitoring indicated fetal distress, completion of lung maturity was not possible and a repeat cesarean section was performed. A 2950 g male preterm infant was delivered with APGAR scores of 5/8/8 and umbilical cord pH of 6.94/7.04. Retroplacental hematoma confirmed the diagnosis of partial placental abruption assumed because of the fetal heart rate pattern.

Figure 1

Ultrasound with 31+2 weeks of gestation revealed a mass in the right upper arm.

Figure 2

Regularly performed ultrasound controls showed progression of the fetal tumor.

The newborn’s right arm showed a livid tumor that extended from the elbow to the right thoracic wall. Radiography showed an impression of the right hemithorax and a mediastinal shift to the left side. There was an additional retroauricular tumor of 2×2 cm that was assumed to be a metastasis. Because of respiratory exhaustion under non-invasive treatment, the infant had to be intubated 1 h after delivery. As a result of leukocytosis (80.000/μL) and increased C-reactive protein (25 mg/dL), calculated antibiotic treatment with ampicillin and gentamicin was performed until the exclusion of a bacterial infection. In the first days of life, the tumor was progressively growing and tumoral hypervascularization resulted into cardiovascular impairment.

Magnetic resonance imaging (MRI) was performed and showed a soft tissue tumor including the right upper arm and hemithorax (Figure 3). A second retroauricular tumor was of uncertain dignity. There were no distant metastases detectable.

Figure 3

Postnatal magnetic resonance imaging (MRI) shows a heterogeneous hyperintensity of the right arm on T2-weighted MRI.

The biopsy revealed a tumor of high cellularity, containing large aggregates of tumor cells without any architectural characteristics. The large nuclei had a smooth nuclear membrane and bubbly chromatin without signs of rhabdoid morphology. Rate of mitosis was high. About 30% of the investigated area was necrotic and diffuse pattern of infiltration into the adjacent dermis noticed. Immunohistochemistry was negative for markers of rhabdomyosarkoma (myoD1 and myogenin), neuroblastoma (synaptophysin, NeuN, NSE, chromogranin), and Ki-67 labelled nearly 100% of tumor cell nuclei. Investigation by an external pathological referral center for pediatric tumors revealed the malignant extrarenal rhabdoid tumor with nuclear INI-1 negativity. Placental tissue did not show infection or metastases but signs of infarction and matured chorionic villi that pointed to an altered feto-maternal blood exchange.

After the biopsy, the infant showed severe tumoral bleeding of the inoperable tumor with volume deficiency shock that was treated with multiple transfusions of packed red cells, thrombocytes, and fresh frozen plasma. As evidence based treatment options are lacking, a cytostatic treatment with low-dose cyclophosphamide was given for 8 days. After therapy, further tumor progression and ulceration was recognized (Figure 4). As a result of increasing cardiopulmonary decompensation, thrombosis of the inferior vena cava, and a sepsis caused by Enterococcus faecalis, any additional cytostatic treatment was not considered. After detailed dialogue with the parents, therapeutical escalation was not performed and the boy died of multiorgan failure after 26 days.

Figure 4

Progredient tumor mass after taking a biopsy for histopathological examination.

Discussion

Rhabdoid tumors are rare, aggressively growing neoplasms. They were initially described in the kidney but they can also be located at any other part of the body (extrarenal rhabdoid tumor). The typical occurrence is in the first year of life with a predilection for male children (male:female 1.5:1) [6]. An extrarenal rhabdoid tumor, which is already present in utero, is even more likely to show metastases and rapid progression with a high mortality rate. In a systemic review, overall survival of only 9.1% has been described for rhabdoid tumors [5]. Annual incidence among children under 15 years is about 0.19 per million for renal tumors and about 0.32 per million for the extrarenal rhabdoid tumor in the US [3]. T2-weighted MRI usually yields a heterogeneous hyperintensity, however, histopathologic examination is needed to differentiate the tumor’s entity [1]. There might be special cells consisting of a prominent nucleus and eosinophilic inclusions. Furthermore, the tumor can show inactivation of INI-1, a member of the SWI/SNF chromatin remodeling complex located on chromosome 22q11.2, which seems to be typical for the malignant rhabdoid tumor [2].

In this case, a fetal tumor of the right arm was diagnosed at 32 weeks of gestation. Prenatal parental counseling was limited by the fact that sonographic assessment was restricted by maternal adipositas and unavailable histopathologic diagnosis. Differential diagnosis included lymphangioma or rhabdomyosarcoma. In the course of gestation, ultrasound examinations pointed to a malignant mass as rapid tumor growth was observed. Postnatally, histopathologic examination revealed an inactivation of INI-1 and the final diagnosis of an extrarenal rhabdoid tumor. Our ultrasound findings are comparable to one of the cases described by Hösli et al. [4].

In summary, these tumor entities are difficult to detect and to classify in utero but should be kept in mind as a differential diagnosis. As they occur late in pregnancy, and show fast tumor progression treatment options are restricted. It is important to diagnose them as early as possible in regard to the delivery mode and organization of postnatal care, as well as the mental preparation of the parents. Nevertheless, an evidence based treatment is not available and the outcome is poor.