Clinical Futures

• Neuroblastic tumors: ~15% of neoplasms in children <4 years, and > 90% cases diagnosed > 5 years, most common solid neoplasm outside the central nervous system in children.

• Neuroblastic tumors are of the sympathetic nervous system that originate from neural crest sympathogonia, 

• Neuroblastic tumors include ganglioneuromas, ganglioneuroblastomas and neuroblastomas.

• These tumors can grow wherever sympathetic nervous tissue is found, but they most frequently occur in the abdomen. Common locations include the adrenal gland, paraspinal retroperitoneum (sympathetic ganglia), posterior mediastinum, head, and neck. Locations such as the urinary bladder, bowel wall, abdominal wall, and gallbladder are considered unusual.

• Composite neuroblastic tumors have been described. These tumors may have malignant nerve-sheath or pheochromocytoma tumors growing within them. In rare cases, von Recklinghausen disease, Beckwith-Wiedemann syndrome, Hirschsprung disease, central failure of ventilation, and DiGeorge syndrome are associated with ganglioneuroma and ganglioneuroblastoma.

Gross Findings

• All neuroblastic tumors look similar grossly and .the main difference is that ganglioneuroblastoma and neuroblastoma.may have distant metastases. Grossly, they appear as well-circumscribed, smooth or lobulated masses.The cut surface may be hemorrhagic (neuroblastic tissue), tan (stroma), or necrotic. Up to 30% of these tumors may show calcifications.

• Ganglioneuromas average 8 cm in size and have a pseudocapsule. They are firm to the touch and have a light color ranging from white to yellow. Internally, the tumor may have a whorled appearance with trabeculae.

Microscopic Findings

• The primary histologic features of these tumors are neuroblasts (immature, undifferentiated sympathetic cells), ganglion cells (mature cells), Schwann cells, and stroma (tissue surrounding the ganglion cells). Secondary histologic features include necrosis, mitosis, hemorrhage, fibrosis, calcification, lymphocytic infiltrate, and karyorrhexis (fragmentation of cellular nuclei that usually symbolizes cell death).

• Neuroblastomas consist predominantly of neuroblasts, where ganglioneuromas are composed entirely of well-differentiated cells. Ganglioneuroblastomas contain about 50% or more mature cells. Malignant potential is proportional to the percentage of immature cells in the tumor with neuroblastomas being the most malignant of the three and ganglioneuromas being benign.

• Ganglioneuromas are mature tumors and do not have immature elements, and they have a mixture of ganglion cells and Schwann cells. The presence of neuroblasts automatically makes the tumor a ganglioneuroblastoma or neuroblastoma.

Subtypes

Ganglioneuromas

• Tumors of adolescents and young adults (40-60%), mean age  7 years. Can grow almost anywhere along the paravertebral sympathetic ganglia and in the adrenal medulla.

• Rare, benign, fully differentiated tumors. Contain mature Schwann cells, ganglion cells, fibrous tissue, and nerve fibers. These tumors have no immature elements (such as neuroblasts), atypia, mitotic figures, intermediate cells, or necrosis. In fact, the presence of any these tissue characteristics excludes the diagnosis of ganglioneurom.

• These tumors can arise de novo and result from the maturation of a ganglioneuroblastoma or neuroblastoma into a ganglioneuroma. They may also develop within a neuroblastoma treated with chemotherapy. Metastases in these tumors are exceedingly rare. Metastasis is thought to be the end result of matured ganglioneuroblastoma or neuroblastoma metastases rather than true ganglioneuroma metastases. Bone is the most common site of metastasis. Up to 60% of patients have a bone metastasis at the time of presentation. Bone metastasis accompanied by limping and irritability is called Hutchinson syndrome. Pepper syndrome is the presence of large liver metastases in infants. In children younger than 1 year, skin metastases are common. These metastases occur as darkly pigmented masses resembling blueberries (blueberry muffin syndrome). The lung, dura, and brain are considered unusual locations for metastases

• Usually asymptomatic regardless of their size. These tumors may be hormonally active, and hypertension, diarrhea, flushing, and virilization may occur as a result the secretion of catecholamine, vasoactive intestinal polypeptide, or androgenic hormone. As many as 37% of ganglioneuromas secrete catecholamines.

• Overall, patients with ganglioneuroma have a favorable prognosis.

• Ganglioneuroblastomas most commonly occur in infants and young children and almost never occur after age 10 years. Ganglioneuroblastoma and neuroblastoma tend to occur in young children with the median age of 2 years.

• Ganglioneuroblastomas are a mix of malignant neuroblastoma and benign ganglioneuroma, and they are sometimes called transitional tumors. These lesions also originate from sympathetic cells. Histologically, they are considered malignant because they contain primitive neuroblasts along with mature ganglion cells.

• Ganglioneuroblastomas have a propensity for secreting catecholamines, and approximately 90-95% actively secrete vanillylmandelic acid (VMA) and homovanillic acid (HVA). HVA tends to be secreted by more mature and differentiated tumors, and VMA is usually a product of less differentiated tumors. In fact, the ratio of VMA to HVA can be used to assess tumor maturity, thereby being a prognostic factor. In addition, more mature tumors may contain vasoactive intestinal peptide (VIP) producing ganglion cells.

• Despite these possible comorbidities, the prognosis for patients with a ganglioneuroblastoma is still relatively good. These tumors can spontaneously regress or mature. In fact, all ganglioneuromas are thought to have once been ganglioneuroblastomas/neuroblastomas at an earlier stage of their development. Regression has an unknown cause and occurs in 1-2% of tumors.

• Patients with ganglioneuroblastomas often present with pain caused by either the primary tumor or metastatic disease and abdominal distention. Patients may also complain of irritability, weight loss, malaise, shortness of breath, peripheral neurologic symptoms (nerve or nerve root compression), and Horner syndrome (ptosis, myosis, and ipsilateral anhydrosis).

Reference

• Rha SE, Byun JY, Jung SE, et al: Neurogenic tumors in the abdomen: tumor types and imaging characteristics. Radiographics 2003 Jan-Feb; 23(1): 29-43

• http://www.webpathology.com/ (For gross and slides of ganglioneuroma)

• http://www.emedicine.com/radio/topic293.htm

• http://www.emedicine.com/RADIO/topic472.htm

• http://enjoypath.com/sp/case-37/case-37.htm