Signs and symptoms of neuroblastoma vary with the site of development of the tumor and can mimic other diseases due to its extreme clinical variability, with an increase in diagnostic complexity. Neuroblastomas can be initially asymptomatic and can be discovered as an incidental radiological finding, or can cause symptoms from catecholamine secretion, mass effect or metastatic spread. Sign and symptoms of abdominal tumors, which represent approximately two thirds of primary neuroblastomas, may include abdominal mass, abdominal pain or fullness, constipation and urinary retention. Moreover, large tumors can cause a compression of the venous and lymphatic drainage and of the renal artery, leading to hypertension. Neuroblastoma metastasizes by both lymphatic and hematogenous routes and almost 40% of neuroblastomas are metastatic at diagnosis. Hematogenous spread extends most often to bone, causing bone pain especially during ambulation, bone marrow, leading to cytopenia, skin, and liver, rarely to lung and brain parenchyma. Metastatic involvement of the liver is common in infants and can cause respiratory compromise.
Musculoskeletal symptoms may occur in up to 25% of pediatric cancers and joint involvement may be present in 16% of cases. Limping is the most common manifestation, but other bones may be involved, causing different medical complaints. In fact, neuroblastoma affects bones in 21% of cases(3,4), almost as much as leukemia, which is the tumor that most frequently involves the bone structure (excluding primary bone cancers). Lytic bone lesions have been described in metastatic neuroblastoma due to the activation of osteoclasts.
Therefore, there is a high risk of diagnostic delay and misdiagnosis. Factors that can help to discriminate malignancies from rheumatic disease are: limb and back bone pain, night pain, refusal to walk, arthropathy of the hip and the cervical spine, pain disproportionate to physical findings, and a discrepancy between inflammation signs (fever, arthritis) and the expected increase of blood cells count with relatively low WBC (in the range of 5000 mmc) and platelets (in the range of 100.000 mmc)(4).
Neuroblastoma is diagnosed on the basis of histological examination, combined with chemical profiling and imaging findings(6). Ultrasounds are usually the first step to evaluate a child with a suspected abdominal mass, but a CT scan or an MRI are necessary to characterize the primary tumor and localize regional and distant metastases. Blood tests could show cytopenia, due to bone marrow infiltration. Raised serum levels of Neuron-Specific Enolase have been found in all stages of neuroblastoma, although the incidence of increased concentration is greater in widespread and metastatic disease(7). More than 90% of individuals with neuroblastoma also present elevated levels of VMA and HVA at the 24-hours urine collection and in single spot urines. To have a whole-body disease assessment, I-123 metaiodobenzylguanidine (mIBG) scintigraphy and bone marrow aspiration can also be performed.
Children with neuroblastoma could have widely different outcomes. In fact, neuroblastomas are remarkable for their broad spectrum of clinical behavior, which can range from spontaneous regression to aggressive disease with metastatic dissemination. According to the International Neuroblastoma Risk Group (INRG) staging system, patients can be partitioned into 4 risk groups for treatment. Patients with low- and intermediate-risk disease are variably treated with surgical resection or moderate doses of chemotherapy followed by surgical resection. Infants with stage 4S/MS neuroblastoma may undergo spontaneous regression. Current standard treatment for high-risk patients includes 4 treatment blocks: induction with chemotherapy, surgery on primary site of disease, consolidation involving the administration of high dose chemotherapy combined with autologous stem cell transplantation and radiotherapy, and maintenance with immunotherapy and 11 cis-retinol(8).
This case shows that the presence of torticollis could be a chief complaint of neuroblastoma. In a child with an unexplainable torticollis, we should always consider bone involvement by a metastatic neuroblastoma. In fact, osteolytic lesions may be indicator of metastatic neuroblastoma.
To our knowledge, neuroblastoma is not mentioned among life-threatening underlying conditions of torticollis in most recent literature reviews(9). In fact, while posterior fossa tumors are always suspected in front of torticollis in infants, torticollis is not usually considered as an alarming sign of possible neuroblastoma. In a cohort study in which 392 pediatric patients with torticollis were enrolled, none had neuroblastoma(10).
This case reminds general practitioners that in presence of unexplained torticollis in a toddler a neuroblastoma should be ruled out. Pediatricians play a crucial role in the diagnosis of neuroblastoma and should be aware of the multitude of clinical manifestations of this elusive tumor(3).