Ganglioneuroblastoma is an uncommon peripheral neuroblastic tumor. The International Neuroblastoma Pathology Classification, popularly known as the Shimada system, grades these into four distinct categories based upon the histopathological balance between neural-type cells (primitive neuroblasts, maturing neuroblasts, and ganglion cells) and Schwann-type cells (Schwannian-blasts and mature Schwann cells). These include neuroblastomas (Schwannian stroma-poor), ganglioneuroblastoma intermixed (Schwannian stroma-rich), ganglioneuroma (Schwannian stroma-dominant) and ganglioneuroblastoma nodular (composite Schwannian stroma-rich/stroma-dominant and stroma-poor) and neuroblastic tumors unclassifiable [3
Ganglioneuroblastoma have intermediate malignant potential, between that of neuroblastomas and ganglioneuromas. Histologically, they are considered malignant because they contain primitive neuroblasts along with mature ganglion cells. In contrast, their benign counterparts, ganglioneuromas are fully differentiated tumors that contain all mature cell types but lack the immature elements (such as neuroblasts), atypia, mitotic figures, intermediate cells, or necrosis [4
Ganglioneuroblastomas occur with equal frequency in both the genders and most commonly in babies and in young children, with occurrence after 10 years of age being extremely rare [4
]. They occur most commonly in the adrenal medulla, extra-adrenal retroperitoneum, and posterior mediastinum, with the neck and pelvis being less common sites of occurrence [5
]. Thus, the occurrence of a posterior mediastianal ganglioneuroblastoma in our eight-year-old patient made this a rarity.
When dealing with pediatric masses, differentials such as rhabdomyosarcomas, Wilms tumor, germ cell tumors, and so on, should be taken into consideration. Rhabdomyosarcoma is the most common soft tissue sarcoma in children and usually originates in the head and neck (28%), extremities (24%), and genitourinary (GU) tract (18%). The cause is unclear; however, several genetic syndromes such as neurofibromatosis, Li-Fraumeni syndrome, and so on, are associated with it. Symptoms usually depend on the location and the tumours usually present as an expanding mass. Wilms tumor, by contrast, is the most common cancer of the kidneys in children. The majority are unilateral, encapsulated, vascularized, and usually do not cross the midline of the abdomen. They can go undetected early on because the tumor can grow large without causing pain. Children usually present with abdominal swelling or blood in the urine.
Patients with ganglioneuroblastoma often present clinically with pain caused by either the primary tumor or by metastatic disease. Patients with mediastinal tumors can present with stridor and shortness of breath secondary to tracheal deviation or narrowing. Large thoracic tumors can cause mechanical obstruction resulting in superior vena cava syndrome. Nerve or nerve root compression by the mass can result in peripheral neurological signs. Patients with cervical masses can present with Horner's syndrome [6
]. However, in our patient these classical signs and symptoms were not present and the only complaint was that of non-specific lumbar pain.
Histological confirmation is required for definitive diagnosis. Tissue is obtained by incisional biopsy of the primary tumor or bone marrow trephine/aspirate in patients suspected of having metastatic disease in the bone marrow.
The most common site for metastasis in ganglioneuroblastomas is bone, which may mean patients present with limping and unexplained irritability (Hutchinson's syndrome). Another site of metastasis is the liver. Pepper syndrome is the presence of large liver metastases in babies such that intra-abdominal pressure becomes so high that there might be possibility of respiratory compromise. In children younger than a year old, skin metastases are common, which are darkly pigmented masses resembling blueberries (hence it is called 'blueberry muffin' syndrome) [7
]. In our patient, investigation was performed to rule out metastasis and was found to be negative.
A CT scan is the imaging modality of choice to evaluate neuroblastic tumors. There is enough evidence to suggest that it is superior both in terms of determining tumor size and other characteristics including organ of origin, tissue invasion, vascular encasement, lymphadenopathy, and calcifications [5
The prognosis for patients with localized disease and younger age is better; several screening programs were developed for the detection of neuroblastoma in infancy by measuring urinary catecholamines [8
] but were not associated with any difference in mortality. As a result, they are not routinely recommended.
Age is taken into account when defining neuroblastoma histology as favorable or unfavorable. The younger the age at diagnosis, the better the survival rate [8
] with children younger than a year old having considerably better survival than older children. Even the outcome of favorable or less aggressive neuroblastomas is worse in older children [9
]. Hence, although it is not rare in the literature to find reports of good outcomes, the excellent results and successful follow-up in our patient is of significant note.
Mediastinal neuroblastomas are better in terms of prognosis than abdominal neuroblastomas in that patients with the former tend to present earlier when the size is still small, and hence complete resection of the tumor is possible [10
]. Complete excision remains the mainstay of therapy of localized mediastinal neuroblastomas. There are no reports of the recommended duration of follow-up; however, follow-up is required with chest X-ray. The two-year event-free survival rates are 85% to 100%; relapses can be salvaged by further surgery or chemotherapy [11
Differential markers for distinguishing ganglioneuromas from ganglioneuroblastomas at present are not available; immunohistochemical stains with antibodies such as neurofilament, synaptophysin, chromogranin, s-100 and LCA are generally positive in both ganglioneuromas and ganglioneuroblastomas [12
]. However it has been shown on post-mortem histopathology specimens that an epidermal-growth-factor-like protein called delta-like (dlk), which regulates the differentiation of neuroblastoma cell lines, showed stronger expression in the ganglioneuroma cell lines and weaker expression in ganglioneuroblastoma cell lines [13
], probably suggesting the loss of this differentiation factor in the progress toward the malignant disease.