The occurrence of symptoms of spinal epidural compression (SEC) in an otherwise healthy child constitutes an emergency requiring prompt diagnosis and appropriate treatment. It is the result of an either benign or malignant paravertebral tumor entering the spinal canal through intervertebral foramina (1). Peripheral neuroblastic tumors (PNTs) are by far the commonest histotypes leading to SEC (2, 3). As PNTs are the most frequent tumor in infancy (2), the probability of their etiologic involvement when SEC occurs in the first year of life is even higher (4). Tumor-related SEC is rarely detected in a newborn, with approximately 15 cases described so far, almost all diagnosed with a PNT (5, 6). Here, we describe the case of a newborn presenting at birth with symptomatic SEC; the case was initially thought to be a PNT but was eventually diagnosed as a malignant rhabdoid tumor (MRT). This is possibly the first reported case of this association at birth.

A female Caucasic newborn was normally delivered by a 28-year-old woman after 38 (+5) weeks of an uncomplicated pregnancy. Prenatal ultrasound examinations did not show abnormal findings. Birth weight was 3,170 g. The mother had previously had two spontaneous pregnancies, interrupted for undefined reasons at the 5th and 28th (+4) weeks of gestation. The parents were unrelated and healthy. Family history included breast cancer in a paternal aunt, intestinal polypoid tumor in the paternal grandfather and lung cancer in the paternal grandmother, a heavy smoker. Physical examination at birth revealed a palpable right lumbar paraspinal, mild facial dysmorphism with sloping forehead and dysplastic ears, and two hernias of the abdominal wall (one laterally and one more anteriorly visible only during crying). In addition, neurological examination showed decreased limb strength and hypoactive reflexes of patellar tendons. No other symptoms were present at birth.

Although a variety of pediatric tumors may occasionally present with SEC associated to a paravertebral mass, PNTs are by far the commonest causative hystotype (1, 2). Indeed, 5%–15% of children diagnosed with a PNT present with symptoms of SEC; more than half of these lesions are diagnosed in the first year of life, and, exceptionally, even in neonates (3–6). In the majority of neonates the first symptom was motor deficit, followed by bladder and/or bowel dysfunction. At the last follow-up, they almost invariably suffer the burden of permanent sequelae, in particular motor deficit, with only one patient that had no long-term sequelae (3–6).

As SEC may evolve into paraplegia, chemotherapy must be promptly administered to avoid the establishment of severe sequelae (1). There is worldwide consensus that treatment can be initiated before the histological diagnosis is made, provided that adequate tumor specimens have been secured for pathological and biological investigations. In our case, given the patient's age, the location of the lesion and the imaging characteristics, the tumor was deemed to be a probable PNT, despite the normal urinary catecholamine levels and the patient's dysmorphic features (unusual in PNTs). In the hypothesis of a PNT, the guidelines of the SIOPEN Group (9, 10) state that chemotherapy should be preferred to a neurosurgical approach. However, 48 h after the initiation of therapy, the histological report documented an RT. The chemotherapy program was therefore changed appropriately. Not unexpectedly, the tumor mass underwent rapid progression, resulting in death.

MRT is a highly aggressive neoplasm of infancy and childhood originally described in the kidney and Central Nervous System (CNS) (Atypical Teratoid Rhabdoid Tumors—ATRT). The clinico-pathological spectrum includes other organs, extrarenal soft tissues and skin. The name of these tumors derives from the rhabdoid appearance of the tumor cells, which have large, vesicular nuclei, prominent central eosinophilic nucleoli and abundant eosinophilic cytoplasm. MRT is a polyphenotypic neoplasm with coexpression of Vimentin, at least one epithelial marker (such as Cytokeratin—CK or EMA) neural or neuroectodermal markers such as pS100, GFAP, NSE and synaptophysin, and mesenchimal markers such as MSA, desmin, CD99 and SMA. Myogenin, myoglobin, human melanoma black 45 (HMB-45), chromogranin and CD34 are typically absent. About 75% of MRTs harbor deletions or mutations of the SMARCB1 gene at chromosome 22q11.2 (7, 8, 11). SMARCB1 (SWI/SNF-related, matrix associated, actin-dependent regular of chromatin, subfamily B, member 1) is the protein product of the gene SMARCB1 (also known asINI1 and SFN5) located on chromosome 22q11.2. INI1 is a core subunit of the SW1/SNF ATP-dependent chromatin remodeling complex and is ubiquitously expressed in the nuclei of normal cells; it is thought to function as a tumor suppressor (11). Germline SMARCB1 mutations occur in both familial and sporadic cases. Immunohistochemical analyses for the SMARCB1 protein in MRT of the CNS, kidney and extrarenal soft tissue have shown that absence of protein expression by immunohistochemistry(IHC) (INI1, BAF47) correlates with deletion and mutation of the SMARCB1 gene. The absence of SMARCB1 protein has been detected in a variety of soft tissue tumors, in CNS embryonal tumors without rhabdoid phenotype and in many other entities, indicating the existence of a wider family of SMARCB1-deficient tumors.

The differential diagnosis includes many tumors (Desmoplastic Small Round Cell Tumors—DSRCT, Rhabdomyosarcoma, Synovial sarcoma with rhabdoid features, rhabdomyomatous Wilms' Tumor (12) and, particularly, epithelioid sarcoma, because of the morphological and immunohistochemical overlap of these two tumors. The relationship between these two entities has not yet been clarified; although in the early literature there are contentions that these tumors fall within the same spectrum (13), strong evidence supports the interpretation that proximal-type epithelioid sarcoma and MERT are two distinct entities (14–17). The differential diagnosis is essentially based on clinic-pathological features (age, site), IHC (CD34 reactivity, analysis of specific markers of skeletal muscle differentiation etc.) and genetic features.

As usually occurs in the case of MRT, the neoplastic cells of our patient presented genetic alterations affecting the INI1/hSNF5/SMARCB1 tumor-suppressor gene located 22q11.2. Although several treatment regimens have been tested to improve the grim outcome of MRT patients, less than 30% survive, with a median survival time of 10 months (18–20). Perinatal RTs have an even worse prognosis (20, 21). In the case of extracranial RT, young age (<1 year) and male gender are also negative prognostic factors (20).

The discovery of MRT associated to SEC is rare: in a review, Babgi et al. describe a case of spinal MRT with an intra- and extramedullary lesion in the thoracolumbar region, treated with a combination of surgery, systemic chemotherapy and radiotherapy; the patient survived for about 16 months. An additional 25 cases with spinal structure involvement are reported in the review. Radiological characterization was available in only 11 cases, 10 of which were described as extramedullary intradural lesions and one as extramedullary intradural lesion. Management was reported for only 16 patients: surgery was performed in 11, adjuvant chemotherapy was administered to all, and nine received radiotherapy. Survival information was reported in 17 cases; 13 died, the median survival time being 10 months (22). In addition, a 2016 paper describes 100 cases of extracranial RT, 14 of which had a paraspinal localization and one had metastatic disease. This cohort included 13 patients with congenital RT, all of whom died. Five of these had metastatic disease and most had a lesion >5 cm. The main sites of primary disease were: paraspinal, thoracic, retroperitoneal, and hepatic. It is possible that these patients had a germline mutation of the SMARCB1 gene, but these data are not present in the review (20).

The presence of dysmorphic features in a newborn diagnosed with a tumor prompted us to perform appropriate genetic analyses. To exclude RT predisposition syndrome (23), genomic DNA was isolated from the patient's peripheral blood and analysis of the coding sequenceof INI1gene was carried out. Constitutional DNA was used for MLPA analysis to detect abnormal copy numbers of the gene locus. Neither MLPA analysis nor HSNF5/INI1 gene sequencing on the patient's constitutional DNA revealed genetic alterations, thus excluding RT predisposition syndrome. Array CGH analysis on the child's DNA identified a 10q21.3 deletion of 81.28 kb, transmitted by her healthy mother. This deletion interval could have been responsible for the patient's dysmorphic features, and the same overlapping interval could account for both developmental delay and mental disability (24). This deletion interrupted the CTNNA3 gene, which is the most recently characterized member of the alpha catenin family. CTNNA3, a cell-cell adhesion gene, encodes a protein of 895 amino acids; in hepatocellular carcinoma (HCC), this works as a tumor suppressor (25). CTNNA3 is reported to inhibit the proliferation, migration and invasion of HCC cell lines. In addition, the mother's DNA carried a 3p13 deletion of 68.92 kb (71772963–71841921) containing the PROK2 gene, a gene responsible for type-4 Kallman syndrome, or isolated GnRH deficiency without anosmia (26), although the mother is healthy and normosomic.

In conclusion, we describe the case of a newborn who, at birth, presented dysmorphic features and neurological deficit of limbs secondary to invasion of the spinal canal by a paravertebral tumor mass, which turned out to be a malignant rhabdoid tumor. As expected, despite prompt specific treatment, the clinical course was rapidly fatal.