Maturation of Neuroblastoma to Ganglioneuroma

Abstract

A neuroblastoma transformed into a ganglioneuroma was well studied by the use of large sections which allowed the observation of the actual transformation of one element into the other. Despite extensive therapy and despite the presence of large areas of maturation the child died with widespread neuroblastomatous metastases. The attention of pathologists and clinicians is again directed to the necessity of studying such cases in detail, in order to comprehend fully the factors involved in the intriguing question of maturation of neuroblastomatous tumors.Although the possibility of maturax\. tion of a "neuroblastoma" into a "ganglioneuroma" is one of the most debated and most intriguing fea¬ tures of this tumor, the actual num¬ ber of cases in which this transition has been demonstrated is dis¬ appointingly small. Potter,1 who quotes the case of Potter and Parrish,2 and Willis3·4 both state that such instances are rare. Dyke and Mulkey,5 who have presented a case of their own, consider that there have been only four instances previ¬ ously described, although there are a few other cases which are less well documented. Wilkerson et al,6 on the other hand, found ten such instances in the literature. Everson and Cole,7 who have reviewed instances of spontaneous regression of neuroblas¬ toma, state that five of their 29 col¬ lected cases showed maturation of neuroblastoma to ganglioneuromas.In view of the few well documented instances, it was, therefore, consid¬ ered of interest to report another instance of a neuroblastoma with ex¬ tensive areas of ganglioneuromatous character, in the hope of stimulating other workers to record their experi¬ ences, since there can hardly be a pa¬ thologist or clinician who has not been, at one time or another, made to ponder this intriguing question. Clinical HistoryA 7-year-old white girl developed an ab¬ dominal mass which was diagnosed on clinical and hematological grounds as a neuroblastoma. She was treated with radi¬ ation to the chest, abdomen, and pelvis, and with cyclophosphamide (Cytoxan) and vincristine sulfate. At the exploratory laparotomy, undertaken when the abdominal swelling had markedly decreased in size, the left kidney was found to be encased in a tumor mass which included the aorta and the vena cava and extended from the area of the left kidney up to the lesser peritoneal sac to the level of the dia¬ phragm. A biopsy taken at this time confirmed the diagnosis of a neuroblas¬ toma, which now showed much necrosis and calcification. At this time numerous bony as well as pulmonary métastases were present. The child was subsequently admitted on several occasions for further treatment by radiation, chemotherapy, and blood transfusions. Her final admis¬ sion was seven months after she had first been seen. The patient now had become very weak and lethargic, and complained of increasing loss of weight. She was found to be very cachectic, with marked anemia (hemoglobin, 3.2 gm/100 cc; white blood cell count, 2,600/cu mm; differential count, 86% polymorphonuclear leukocytes)....

Does Horner's syndrome in infancy require investigation?

“…Ganglioneuroma has been reported as a rare cause of infantile Horner’s syndrome 1112 These tumours are thought to represent a regressed form of neuroblastoma and if left untreated the outcome would probably have been good 1718…”

Thoracic paravertebral ganglioneuroma with high immunohistochemical expression of TrkA

“…5,6 Alternatively, it may be possible that our paravertebral tumor was a metastasizing tumor from the original retroperitoneal ganglioneuroblastoma, which had matured into a well-differentiated ganglioneuroma. Several reports have indicated that the malignant forms of neuronal cell tumors are capable of maturation to benign forms, specifically to ganglioneuromas, [13][14][15][16][17] and that such maturation has also been reported at sites of metastasis. 11 In regard to the regression and maturation of neuronal cell tumors, the product of proto-oncogene Trk (p140 proto-TRK ), also known as TrkA, 7,18 has recently been given an increasing amount of attention.…”

“…Alternatively, it may be possible that our para‐vertebral tumor was a metastasizing tumor from the original retroperitoneal ganglioneuroblastoma, which had matured into a well‐differentiated ganglioneuroma. Several reports have indicated that the malignant forms of neuronal cell tumors are capable of maturation to benign forms, specifically to ganglioneuromas, 13 –17 and that such maturation has also been reported at sites of metastasis 11 …”

Hepatomegaly as a Single Presenting Sign of Stage IV‐S Neuroblastoma

“…Another explanation is spontaneous maturation and involution. Maturation to neurofibroma and ganglioneuroma was discussed by Griffin and Bolande (11) and by Hass et al ( 4), Aterman and Schueller (12), and Dyke and Mulkey (13) , respectively. Hass et al, following an infant with IV-S neuroblastoma by performing repeated biopsies of affected lymph nodes, demonstrated the procession from neuroblastoma to ganglioneuroma and finally to fibrosis (4).…”