Researchers have reported an exceptionally rare case of neuroblastoma in a 35-year-old man whose cancer had spread widely without any identifiable primary tumor, and who was treated with high-dose 131I-MIBG therapy followed by an autologous stem cell transplant. The case, published in Discover Oncology, is paired with a systematic review that found only four previously reported cases of adult-onset neuroblastoma without a detectable primary tumor, none of which had received a stem cell transplant. The report adds a new treatment experience to a disease area so sparse that no standardized treatment protocol exists for adults.

Neuroblastoma is an embryonal tumor that predominantly affects children, with a median age at diagnosis of 17 months. When it arises in adults, it is extremely rare and behaves differently: adult-onset disease shows more aggressive behavior, a poorer prognosis, and a lack of standardized treatment protocols compared with pediatric cases. Cases in which no primary tumor can be found are exceptionally uncommon, and the review authors noted that a parenchymal brain metastasis present at diagnosis makes such presentations even rarer.

The patient in this report first came to medical attention with low back pain, anemia, and an elevated erythrocyte sedimentation rate, a blood marker of inflammation. The diagnostic workup combined several approaches: imaging studies, a core needle biopsy examined with immunohistochemistry, analysis of urinary catecholamine metabolites, and 123I-MIBG scintigraphy, a functional imaging technique that relies on a radioactive tracer taken up by certain neuroendocrine tumor cells. Together these tests established a diagnosis of metastatic neuroblastoma despite the absence of a locatable primary tumor.

Imaging and clinical evaluation showed widely metastatic, MIBG-avid disease involving the bone, bone marrow, pleura, and brain. The tumor’s avidity for MIBG, meaning its tendency to concentrate the iodine-131 labeled tracer, is clinically important because the same biology can be exploited therapeutically with high-dose 131I-MIBG, a targeted radiopharmaceutical that delivers radiation directly to MIBG-avid tumor deposits. In this patient, however, the disease progressed rapidly despite initial chemotherapy given according to a Children’s Oncology Group protocol.

After that progression, the treatment team turned to salvage chemotherapy with the ICE regimen, which combines ifosfamide, carboplatin, and etoposide. The patient then received high-dose 131I-MIBG therapy followed by an autologous stem cell transplantation, a sequence in which the patient’s own blood-forming stem cells are collected and reinfused to restore bone marrow function after intensive treatment. This multimodal approach, spanning protocol chemotherapy, salvage agents, targeted radiotherapy, and transplant, reflects the absence of any established adult standard of care and the need to adapt strategies across pediatric and oncology practice.

Despite the full sequence of therapies, the patient died of pneumonia five months after the transplantation. The authors present this outcome without overstating it: the report documents what happened in a single case, and a fatal infection after intensive treatment does not establish how the treatment strategy would perform across a larger group of patients. With only a handful of adult cases ever described, no controlled evidence exists to define the optimal role of 131I-MIBG therapy or transplantation in this population.

To place the case in context, the researchers conducted a systematic review following PRISMA 2020 guidelines. They searched PubMed, Scopus, Embase, and Web of Science in September 2026 for cases of adult-onset neuroblastoma, defined as age 18 years or older, without a detectable primary tumor. From the literature they extracted data on patient demographics, clinical features, treatment, and outcomes. The search identified four previously reported cases, all in male patients aged 18 to 63 years.

The review revealed marked heterogeneity across those four cases. Clinical presentations, metastatic sites, diagnostic approaches, and treatments all differed from one patient to the next. The treatment modalities recorded in the literature included surgery, radiotherapy, chemotherapy, 131I-MIBG therapy, and targeted therapy. Outcomes were split: two of the four previously reported patients survived, and two died during follow-up. Notably, none of the previously reported patients underwent autologous stem cell transplantation, which makes the current case the first documented pairing of high-dose 131I-MIBG therapy with ASCT in this specific clinical scenario.

The authors conclude that adult-onset neuroblastoma without an identifiable primary tumor is extremely rare, particularly when a parenchymal brain metastasis is present at diagnosis, and that there is no standardized treatment approach. They argue that their case adds practical experience with high-dose 131I-MIBG followed by ASCT and underscores the value of early functional imaging and catecholamine testing, the same tools that ultimately established the diagnosis in their patient. They also call for further evaluation of treatment strategies in adults, a need made concrete by the small, heterogeneous case literature their review assembled.

For clinicians, the practical message is that adult neuroblastoma can present far from its pediatric counterpart, with nonspecific symptoms such as back pain and anemia, and can evade detection of its point of origin entirely. The combination of functional imaging with 123I-MIBG, catecholamine metabolite measurement, and immunohistochemistry on biopsy material proved decisive in this case. As a single-patient report, the findings cannot guide therapy on their own, but they document a treatment sequence not previously recorded in the literature and give researchers a starting point for evaluating whether intensive multimodal approaches, including radiopharmaceutical therapy and transplantation, deserve systematic study in adults with this rare disease.

Subject of Research: A case report and systematic review of adult-onset metastatic neuroblastoma without an identifiable primary tumor, treated with high-dose 131I-MIBG therapy and autologous stem cell transplantation

Article Title: High-dose 131I-MIBG therapy followed by autologous stem cell transplantation in adult-onset metastatic neuroblastoma without an identifiable primary tumor: a case report and systematic review

Article References: Zangeneh, S., Pirouzkhah, M., Khazaeli Najafabadi, M., Emami-Ardakani, A., Salehi, Z., & Rostami, M. (2026). High-dose 131I-MIBG therapy followed by autologous stem cell transplantation in adult-onset metastatic neuroblastoma without an identifiable primary tumor: a case report and systematic review. Discover Oncology. https://doi.org/10.1007/s12672-026-06242-z

Image Credits: AI Generated

DOI: 10.1007/s12672-026-06242-z

Keywords: neuroblastoma, adult-onset cancer, 131I-MIBG therapy, autologous stem cell transplantation, metastatic disease, case report, systematic review, rare cancer, brain metastasis, functional imaging, catecholamines, pediatric versus adult oncology