Diagnosis and treatment of neuroblastoma of the adrenal region in the neonatal period Neuroblastoma (NB) is one of the most common malignant solid tumors in children, accounting for 5% of all pediatric malignancies. 85% occur before the age of 5 years and 75% occur before the age of 2 years. It can be located anywhere in the median axis from the brain to the sacrococcygeal region, and 40% of tumors originate in the adrenal region. However, they occur less frequently in the neonatal period within 3 months of age. Given the characteristics of neonates themselves, surgery and late treatment are very difficult. Since 2005, our hospital has treated 12 cases of neuroblastoma in the adrenal region. Clinical data: 12 cases of NB, 7 males and 5 females, age: 25 days to 3 months, average 1.5 months, all of them with the complaint of “epigastric abdominal occupancy”. Nine of these cases were found during the physical examination of their mothers during pregnancy. The other 3 cases were found inadvertently by ultrasound examination for other diseases, and 1 case was a bilateral adrenal occupancy with multiple subcutaneous nodules on the extremities and trunk, with a “blueberry pie-like” appearance of skin elevation on the surface of the nodules. In all cases, CT examination was performed, and 5 cases were totally solid and 7 cases were cystic solid. The preoperative diagnosis was that the adrenal gland was occupied and intracapsular hemorrhage was more likely. In 11 cases, complete resection of adrenal tumor was performed, and the pathological diagnosis was: adrenal neuroblastoma. 1 case was bilateral, and the family gave up the treatment because of extensive spread of skin. 1.5 years later, the child had good development, no malignant tumor appearance, the whole body “blueberry pie-like” nodules disappeared, and the right adrenal tumor disappeared on CT examination. The tumor on the right side of the adrenal gland disappeared and the left side shrunk by 2/3, which was the natural regression of the tumor. After the surgical treatment, the family members were suggested to further comprehensive treatment for malignant tumor, including chemotherapy or radiotherapy. However, none of the cases underwent relevant treatment. In this paper, 12 patients were followed up, 3 cases were lost, and the follow-up time was 6 months-5 years. 9 cases all survived and no local recurrence or metastasis was seen. Discussion 1. Imaging and pathological characteristics of NB in the neonatal period Imaging characteristics Because of the hidden location of tumors in the adrenal area, they are not detected until they grow to a certain extent and produce compression symptoms. Among the 12 cases in this paper, 9 cases were found during prenatal examination. The other 3 cases were detected during ultrasound examination for other diseases after birth. In tumors originating from the sympathetic chain, the tumors were multinodular and grew along both sides of the spine with nonspecific margins and easily crossed the midline; in these 12 cases, the tumors originated from the adrenal gland and pressed downward on the kidney, and the tumors were round-like with still neat margins, unlike NB originating from the sympathetic chain, which quickly crossed the midline. Pathologic features Seven of the 12 cases of NB showed cystic solid changes on preoperative CT, which were misdiagnosed preoperatively as neonatal adrenal hemorrhage. Intraoperatively, intracapsular hemorrhagic changes were indeed seen. NB in the neonatal period is actually an embryonal tumor, that is, it contains immature tissues in the organs that contain tissue masses of different maturity and composition, some of which are benign and some of which are malignant. As with any malignant tumor treatment, comprehensive treatment includes surgery, chemotherapy and radiation therapy. Surgery is the preferred method for neuroblastoma of the adrenal region in newborns. Once the indication for surgery is found, it should be removed immediately. In fact, surgery in the neonatal period is easier because the tumor is smaller and the surrounding invasion is lighter, so complete resection is easier. However, due to the special anatomical and physiological characteristics of neonates, surgical trauma, anesthesia, blood loss, body temperature and ambient temperature, etc., a holistic approach should be considered and an individualized plan should be formulated to ensure surgical safety. Malignant tumors should be treated with chemotherapy, but chemotherapy should be especially cautious in the neonatal period. In this group, all tumors were completely resected except for one bilateral case, and no chemotherapy was administered in any of the cases, and no recurrence or death was observed during the follow-up period of 6 months to 5 years. The reasons for not performing conventional chemotherapy in these cases are, first, that despite the recommendation of postoperative chemotherapy to the family, the physicians showed a lack of confidence and initiative in this regard; furthermore, parents often do not agree to the implementation of chemotherapy in newborns who have just suffered surgical trauma and are uncertain about their chances of survival. The National Society for Nephroblastoma has been able to achieve the same efficacy with minimal toxicity by applying 50% dose chemotherapy to children with nephroblastoma under 1 year of age. Some institutions in China have even accumulated some experience in treatment by reducing the dose while shortening the course of treatment. Unlike some malignancies where chemotherapy has revolutionized tumor treatment, such as nephroblastoma, complete resection of the tumor in the neonatal period has been curative for NB. Radiotherapy for malignant tumors is extremely damaging to the childhood organism and mostly irreversible. Especially in neonates, it should be avoided. Therefore, the treatment of NB in the neonatal period should be individualized according to tumor size, differentiation degree, lymph node metastasis, and the extent of peripheral invasion. There are case reports of spontaneous regression of neuroblastoma in textbooks and literature, but it is extremely rare in real clinical practice. In the present case, the neonate with bilateral adrenal NB and extensive cutaneous metastases was in clinical stage 4. These tumor nodules were located in the extremities and trunk, forming a characteristic “blueberry pie” appearance. This particular phenomenon suggests that the appearance of skin nodules in NB during the neonatal period is often a sign of good prognosis. As for the mechanism of natural tumor regression, pathologically it is mostly nodular NB or differentiated NB, and the literature points out that most multisite NBs have good biological characteristics and are mostly of special stage 4, as confirmed by studies of NB proliferation index, telomerase activity, MYCN, NTRK1, Ha-ras p21 and DNA content.