Familial neuroblastoma in some cases is caused by rare germline mutations in the anaplastic lymphoma kinase (ALK) gene.

[13] Duplicated segments of the LMO1 gene within neuroblastoma tumor cells have been shown to increase the risk of developing an aggressive form of the cancer.

[18] Other studies have examined possible links with atopy and exposure to infection early in life,[19] use of hormones and fertility drugs,[20] and maternal use of hair dye.

[21][22] The diagnosis is usually confirmed by a surgical pathologist, taking into account the clinical presentation, microscopic findings, and other laboratory tests.

When it is radio-iodinated with I-131 or I-123 (radioactive iodine isotopes), it is a very good radiopharmaceutical for diagnosis and monitoring of response to treatment for this disease.

I-131 has a half-life of 8 days and at higher doses is an effective therapy as targeted radiation against relapsed and refractory neuroblastoma.

[28] On microscopy, the tumor cells are typically described as small, round and blue, and rosette patterns (Homer Wright pseudorosettes) may be seen.

[29] They are also distinct from the pseudorosettes of an ependymoma which consist of tumor cells with glial fibrillary acidic protein (GFAP)–positive processes tapering off toward a blood vessel (thus a combination of the two).

[30] A variety of immunohistochemical stains are used by pathologists to distinguish neuroblastomas from histological mimics, such as rhabdomyosarcoma, Ewing's sarcoma, lymphoma and Wilms' tumor.

This distinction in the pre-treatment tumor pathology is an important prognostic factor, along with age and mitosis-karyorrhexis index (MKI).

Beginning in 2005, representatives of the major pediatric oncology cooperative groups have met to review data for 8,800 people with neuroblastoma treated in Europe, Japan, USA, Canada, and Australia between 1990 and 2002.

Screening asymptomatic infants at three weeks, six months, and one year has been performed in Japan, Canada, Austria and Germany since the 1980s.

Screening was halted in 2004 after studies in Canada and Germany showed no reduction in deaths due to neuroblastoma, but rather caused an increase in diagnoses that would have disappeared without treatment, subjecting those infants to unnecessary surgery and chemotherapy.

Biologic and genetic characteristics have been identified, which, when added to classic clinical staging, has allowed assignment to risk groups for planning treatment intensity.

[44] These criteria include the age of the person, extent of disease spread, microscopic appearance, and genetic features including DNA ploidy and N-myc oncogene amplification (N-myc regulates microRNAs[45]), into low, intermediate, and high risk disease.

Agents commonly used in induction and for stem cell transplant conditioning are platinum compounds (cisplatin, carboplatin), alkylating agents (cyclophosphamide, ifosfamide, melphalan), topoisomerase II inhibitor (etoposide), anthracycline antibiotics (doxorubicin) and vinca alkaloids (vincristine).

Some newer regimens include topoisomerase I inhibitors (topotecan and irinotecan) in induction which have been found to be effective against recurrent disease.

In November 2020, naxitamab was approved for medical use in the United States in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) to treat people one year of age and older with high-risk neuroblastoma in bone or bone marrow whose tumor did not respond to or has come back after previous treatments and has shown a partial response, minor response, or stable disease to prior therapy.

SNP array virtual karyotyping is preferred for tumor samples, including neuroblastomas, because they can detect copy neutral loss of heterozygosity (acquired uniparental disomy).

The characteristics of tumors from the sympathetic nervous system and the adrenal medulla were then noted in 1891 by German pathologist Felix Marchand.

In 1910 James Homer Wright understood the tumor to originate from primitive neural cells, and named it neuroblastoma.

He also noted the circular clumps of cells in bone marrow samples which are now termed "Homer Wright rosettes".

[79] PDX models are more predictive of clinical outcome as compared to conventional cancer cell line xenografts.

[79] Recent focus has been to reduce therapy for low and intermediate risk neuroblastoma while maintaining survival rates at 90%.

Chemotherapy induction variations, timing of surgery, stem cell transplant regimens, various delivery schemes for radiation, and use of monoclonal antibodies and retinoids to treat minimal residual disease continue to be examined.

Recent phase III clinical trials with randomization have been carried out to answer these questions to improve survival of high-risk disease: Chemotherapy with topotecan and cyclophosphamide is frequently used in refractory setting and after relapse.

[94] These two repositories contain data of electronic health records of thousands of patients that are available for scientific research, with prior authorization.