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Incidental ganglioneuroblastoma
PEDIATRIC U OLOGY
INCIDENTAL GANGLIONEUROBLASTOMA DAVID A . DIAMOND, M .D . ROBERT D . JEFFS, M .D . From The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins Hospital, Baltimore, Maryland
ABSTRACT-A case is described in which an incidental ganglioneuroblastoma was discovered at the time of surgical correction of upper pole hydronephrosis secondary to an obstructing ectopic ureterocele in a duplicated system . We believe this is the first case of incidental ganglioneuroblastoma reported in the urologic literature . The management of this patient's disease is discussed as is the entity of incidental neuroblastoma .
We report on an infant with incidental ganglioneuroblastoma which was discovered at the time of surgical correction of upper pole hydronephrosis . We believe this is the first case of incidental ganglioneuroblastoma reported in the urologic literature . Case Report An eleven-week-old white female infant with a history of urinary tract infection at eight weeks of age was seen . An intravenous pyelogram (IVP) performed following initial presentation demonstrated marked hydronephrosis of the left upper pole system, mild hydronephrosis of the left lower pole system, left hydroureter and a normal collecting system on the right side . A filling defect was noted on the left side of the bladder on IVE A voiding cystouretbrogram demonstrated no evidence of reflux, but an abnormality to the left of the bladder neck consistent with a ureterocele was noted (Fig . 1A) . Cystoscopy was performed, and a ureterocele was noted on the left lateral aspect of the bladder neck . The retrograde pyelogram was performed through the gaping orifice of the ureterocele and demonstrated a dilated ureter communicating with the left upper pole system (Fig . 1B) .
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The patient was referred to The Johns Hopkins Hospital for further evaluation . Abdominal examination was noted to be within normal limits and urinalysis demonstrated 2-3 white blood cells per high-power field but no bacteria . A DTPA renal scan demonstrated a normal right kidney and decreased function of the left upper pole segment to 17 per cent of overall function with the left lower pole segment contributing 34 per cent of overall function . After furosemide (Lasix) was administered there was noted to be radionuclide persisting in both the left upper and lower pole collecting systems after thirty minutes (Fig . 2) . Cystoscopy demonstrated a left ureterocele with an orthotopic left ureteral orifice proximal to the ureterocele . The ureterocele had a gaping orifice located at the bladder neck . The right ureteral orifice appeared to be normal . The patient then underwent left flank exploration . The cortex of the upper pole appeared to be grossly normal and no different from the cortex of the lower pole . A kidneypreserving operation was therefore decided on rather than an upper pole heminephrectomy . The ureter from the upper pole was found to be dilated and was dissected distally. The pelvis and ureter from the lower pole were then examined and a 1-cm stenosis was found in the
UROLOCY / MARCH 1986 / VOLUME XXV11, NUMBER 3
(A) VCUG demonstrating abnormal contour of left lateral wall of bladder consistent with ureterocele . (B) Retrograde injection of ectopic ureterocele demonstrating dilated upper pole ureter. FIGURE 1 .
FIGURE 3 .
High-power view of ganglioneuroblastoma with sheets and nests of primitive neuroblasts separated by fibrovascular septi (arrows point to mature ganglion cells) . renal hilum . A renal biopsy of the tipper pole DTPA renal scan thirty minutes after
FIGURE 2 .
furosemide administered demonstrates incomplete washout of radionuclide from both upper and lower pole calyceal systems on left side ; right side washed out . ureteropelvic junction . The lower pole system was then filleted open through the stenotic segment and pyelo-pyeloureterostomy was performed . During the course of the dissection, a 1 .5-cm node-like mass was dissected from the
UROLOGY
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MARCH 1986 / VOLUME XXVII . NUMBER 3
also was done, and a nephrostomy tube and ureteral stent were left in place . The biopsy of the renal specimen demonstrated normal renal cortical tissue without evidence of dysplasia . The tissue submitted as "lymph node" showed neuroblastic proliferation with focal ganglion formation consistent with a ganglioneuroblastoma (Fig . 3) . The presence of mature ganglion cells distinguished this lesion as a more differentiated and less aggressive form of neuroblastoma .
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In 1963, Beckwith and Perrin 2 first used the term in situ neuroblastoma to describe microscopic cell aggregates incidentally found in adrenal glands of newborns as well as of infants up to three months of age . These lesions usually were confined to the adrenal medulla and adrenal cortex . These authors considered the incidental microscopic cell aggregates to be tumor nodules, which were cytologically indistinguishable from malignant neuroblastoma with no demonstrable metastases . Beckwith and Perrin 2 found 13 cases in their retrospective study of autopsy material which constituted an incidence of 1 in 200 autopsies . The authors suggested that these small lesions represented true malignant neoplasms rather than cell rests and some could have become clinically apparent had the host survived . They attributed their observed incidence of 1 in 200 patients, which is 50 times greater than clinically apparent neuroblastoma, to degeneration and regression of these lesions under normal maturational in-
IVP three months postoperative demonstrating good drainage of upper and lower calyceal systems on left side with mild hydronephrosis . FIGURE 4 .
The child underwent a metastatic evaluation which included twenty-four-hour and spot urine specimens for vanillylmandelic acid (VMA) and homovanillic acid (HVA), a bone survey and bone scan, a chest roentgenogram, and an abdominal and chest computerized axial tomography (CAT) scan . Results of all these tests were within normal limits, without evidence of metastatic disease or metabolic tumor activity . The patient's postoperative course was unremarkable . The child was discharged to home to be followed up with urine VMA and HVA every three months and an abdominal CAT scan every six months for a two-year period . At three months, urine HVA and VMA were negative and an IVP demonstrated good drainage of both upper and lower pole calyceal systems on the left side (Fig . 4) . Follow-up evaluation at twenty-one months demonstrated no evidence of disease . Comment Neuroblastoma is the second most frequent tumor that undergoes spontaneous regression .' It is also the most common solid tumor of childhood, and it is not surprising to find incidental neuroblastomas in pediatric autopsy series .
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fluences . In 1969, Guin, Gilbert, and Jones' reported on 11 infants from birth to three months of age who at autopsy had neuroblastoma involving the adrenal gland as an incidental finding . This resulted in a ratio of 1 neuroblastoma in 432 autopsies, In all of their cases the tumor was confined to the adrenal gland without evidence of metastases . In addition, no ganglion cells were noted in their specimens, and there was no evidence of maturation in any of these tumors . These authors also noted that the increased autopsy incidence relative to the clinical incidence of neuroblastoma suggested that some of these tumors do regress, but the factors that determine whether the tumor would regress or continue to proliferate are unknown . In 1974 Turkel and Itabashi" examined adrenal glands from 92 fetuses from ten to thirty weeks' gestation . These authors found that all glands contained neuroblastic nodules, which they concluded were an integral part of the normal morphogenesis of the adrenal gland, and were not representative of malignant tumors . They noted that these nodules were most common in fetuses of seventeen to twenty weeks' gestation, and the largest were 200 to 400 t in diameter. In addition, the migrational pathway of the neuroblastic nodules was traced from the perivertebral sympathetic ganglia to the periadrenal sympathetic collections . These authors concluded that the neuroblastic nodules
UROLOGY
MARCH 1986 / VOLUME XXVII . NUMBER 3
increased to a certain maximal number and then coalesced or disappeared by early infancy . Unfortunately their study was not carried beyond thirty weeks' gestation . In 1979 Gibbons and Ducketts described a case of neuroblastoma which masqueraded as a UPJ obstruction at three days of age . However, by day 5 the abdominal mass had grown threefold, and the clinical impression changed from one of mild hydronephrosis to that of a flank tumor. Abdominal exploration demonstrated the mass to be an extra-adrenal neuroblastoma which had encased the kidney and ureter . Although we can only speculate on the biologic potential of this lesion, on the basis of the size of the ganglioneuroblastoma (1 .5 cm) in our patient aged eleven weeks, it seemed unlikely that this was a lesion that was about to regress spontaneously . The presence of ganglia, indicating some differentiation of the lesion, suggested a better prognosis for this particular form of neuroblastoma . In their histologic evaluation of 83 patients with neuroblastoma, Hughes, Marsden, and Palmere demonstrated a three-year crude survival rate of approximately 70 per cent of patients with mature ganglion cells in their tumor as opposed to less than 10 per cent in those patients with no evidence of differentiation within the neuroblastoma . Evans et al . in 19767 described the prognostic factors involved with localized neuroblastoma based on their series of 113 patients . Of 27 patients with fully resected Stage 1 disease (disease confined to the organ of origin), the authors noted no recurrences . In addition, they noted that survival was greater than 90 per cent in the first and second years of life and fell to 4 7 per cent if the child was older than two years of age . Of 55 children less than one year of age, 4 recurrences were noted . Evans found that the
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location of the primary tumor above or below the diaphragm was not significant with regard to tumor recurrence and that all patients who relapsed did so within one year . Goldman et al . in 19808 confirmed Evans' findings that stage and age of presentation were important prognostic indicators for neuroblastoma . In addition, they also found that there was improved prognosis if the primary neuroblastoma was of nonadrenal origin . It is uncertain that this incidentally discovered ganglioneuroblastoma would ever have become clinically manifest . However, according to the standard criteria for evaluating neuroblastoma including histologic differentiation, stage of disease, nonadrenal location of primary tumor and age of discovery, our patient's prognosis is a good one . University of Massachusetts Medical Center 55 Lake Avenue North Worcester, Massachusetts 01605 (DR. DIAMOND) References
Katz SE, and Schapira HE : Spontaneous regression of genitourinary cancer-an update, j Urol 128 : 1 (19821 . 2. Beckwith JB, and Perrin E V: In situ neuroblastomas : a contribution to the natural history of neural crest tumors, Am J Pathol 43: 1089 (1963) . 3 . Gum GH. Gilbert EF, and Jones B : Incidental neuroblastomas in infants, J Clin Pathol 51 : 126 (1969) . 4 . Market SB, and Itabashi HH : The natural history of neuroblastic cells in the fetal adrenal glands, Am J Pathol 76 : 25 1.
(1974) . 5 . Gibbons
MD, and Duckett JW : Neuroblastomas masquerading as congenital ureteropelvic junction obstruction, j Pediatr Surg 14 : 420 (1979) . 6 . Hughes M, Marsden MB . and Palmer MK : Histologic patterns of neuroblastoma related to prognosis and clinical staging, Cancer 34 : 1706 (1974) . 7 . Evans AE . et al : Factors influencing survival of children with nonmetastatic neuroblastoma, ibid 38 : 661 (1976) . 8 . Coldman AJ, Fryer CJH, Elwo od JM, and Sonlev MJ : Neurohlastoma influence of age at diagnosis, stage ., tumor site, and sex on prognosis, ibid 46 : 1996 (1980) .
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INCIDENTAL GANGLIONEUROBLASTOMA DAVID A . DIAMOND, M .D . ROBERT D . JEFFS, M .D . From The James Buchanan Brady Urological Institute, and Department of Urology, The Johns Hopkins Hospital, Baltimore, Maryland
ABSTRACT-A case is described in which an incidental ganglioneuroblastoma was discovered at the time of surgical correction of upper pole hydronephrosis secondary to an obstructing ectopic ureterocele in a duplicated system . We believe this is the first case of incidental ganglioneuroblastoma reported in the urologic literature . The management of this patient's disease is discussed as is the entity of incidental neuroblastoma .
We report on an infant with incidental ganglioneuroblastoma which was discovered at the time of surgical correction of upper pole hydronephrosis . We believe this is the first case of incidental ganglioneuroblastoma reported in the urologic literature . Case Report An eleven-week-old white female infant with a history of urinary tract infection at eight weeks of age was seen . An intravenous pyelogram (IVP) performed following initial presentation demonstrated marked hydronephrosis of the left upper pole system, mild hydronephrosis of the left lower pole system, left hydroureter and a normal collecting system on the right side . A filling defect was noted on the left side of the bladder on IVE A voiding cystouretbrogram demonstrated no evidence of reflux, but an abnormality to the left of the bladder neck consistent with a ureterocele was noted (Fig . 1A) . Cystoscopy was performed, and a ureterocele was noted on the left lateral aspect of the bladder neck . The retrograde pyelogram was performed through the gaping orifice of the ureterocele and demonstrated a dilated ureter communicating with the left upper pole system (Fig . 1B) .
254
The patient was referred to The Johns Hopkins Hospital for further evaluation . Abdominal examination was noted to be within normal limits and urinalysis demonstrated 2-3 white blood cells per high-power field but no bacteria . A DTPA renal scan demonstrated a normal right kidney and decreased function of the left upper pole segment to 17 per cent of overall function with the left lower pole segment contributing 34 per cent of overall function . After furosemide (Lasix) was administered there was noted to be radionuclide persisting in both the left upper and lower pole collecting systems after thirty minutes (Fig . 2) . Cystoscopy demonstrated a left ureterocele with an orthotopic left ureteral orifice proximal to the ureterocele . The ureterocele had a gaping orifice located at the bladder neck . The right ureteral orifice appeared to be normal . The patient then underwent left flank exploration . The cortex of the upper pole appeared to be grossly normal and no different from the cortex of the lower pole . A kidneypreserving operation was therefore decided on rather than an upper pole heminephrectomy . The ureter from the upper pole was found to be dilated and was dissected distally. The pelvis and ureter from the lower pole were then examined and a 1-cm stenosis was found in the
UROLOCY / MARCH 1986 / VOLUME XXV11, NUMBER 3
(A) VCUG demonstrating abnormal contour of left lateral wall of bladder consistent with ureterocele . (B) Retrograde injection of ectopic ureterocele demonstrating dilated upper pole ureter. FIGURE 1 .
FIGURE 3 .
High-power view of ganglioneuroblastoma with sheets and nests of primitive neuroblasts separated by fibrovascular septi (arrows point to mature ganglion cells) . renal hilum . A renal biopsy of the tipper pole DTPA renal scan thirty minutes after
FIGURE 2 .
furosemide administered demonstrates incomplete washout of radionuclide from both upper and lower pole calyceal systems on left side ; right side washed out . ureteropelvic junction . The lower pole system was then filleted open through the stenotic segment and pyelo-pyeloureterostomy was performed . During the course of the dissection, a 1 .5-cm node-like mass was dissected from the
UROLOGY
/
MARCH 1986 / VOLUME XXVII . NUMBER 3
also was done, and a nephrostomy tube and ureteral stent were left in place . The biopsy of the renal specimen demonstrated normal renal cortical tissue without evidence of dysplasia . The tissue submitted as "lymph node" showed neuroblastic proliferation with focal ganglion formation consistent with a ganglioneuroblastoma (Fig . 3) . The presence of mature ganglion cells distinguished this lesion as a more differentiated and less aggressive form of neuroblastoma .
255
In 1963, Beckwith and Perrin 2 first used the term in situ neuroblastoma to describe microscopic cell aggregates incidentally found in adrenal glands of newborns as well as of infants up to three months of age . These lesions usually were confined to the adrenal medulla and adrenal cortex . These authors considered the incidental microscopic cell aggregates to be tumor nodules, which were cytologically indistinguishable from malignant neuroblastoma with no demonstrable metastases . Beckwith and Perrin 2 found 13 cases in their retrospective study of autopsy material which constituted an incidence of 1 in 200 autopsies . The authors suggested that these small lesions represented true malignant neoplasms rather than cell rests and some could have become clinically apparent had the host survived . They attributed their observed incidence of 1 in 200 patients, which is 50 times greater than clinically apparent neuroblastoma, to degeneration and regression of these lesions under normal maturational in-
IVP three months postoperative demonstrating good drainage of upper and lower calyceal systems on left side with mild hydronephrosis . FIGURE 4 .
The child underwent a metastatic evaluation which included twenty-four-hour and spot urine specimens for vanillylmandelic acid (VMA) and homovanillic acid (HVA), a bone survey and bone scan, a chest roentgenogram, and an abdominal and chest computerized axial tomography (CAT) scan . Results of all these tests were within normal limits, without evidence of metastatic disease or metabolic tumor activity . The patient's postoperative course was unremarkable . The child was discharged to home to be followed up with urine VMA and HVA every three months and an abdominal CAT scan every six months for a two-year period . At three months, urine HVA and VMA were negative and an IVP demonstrated good drainage of both upper and lower pole calyceal systems on the left side (Fig . 4) . Follow-up evaluation at twenty-one months demonstrated no evidence of disease . Comment Neuroblastoma is the second most frequent tumor that undergoes spontaneous regression .' It is also the most common solid tumor of childhood, and it is not surprising to find incidental neuroblastomas in pediatric autopsy series .
256
fluences . In 1969, Guin, Gilbert, and Jones' reported on 11 infants from birth to three months of age who at autopsy had neuroblastoma involving the adrenal gland as an incidental finding . This resulted in a ratio of 1 neuroblastoma in 432 autopsies, In all of their cases the tumor was confined to the adrenal gland without evidence of metastases . In addition, no ganglion cells were noted in their specimens, and there was no evidence of maturation in any of these tumors . These authors also noted that the increased autopsy incidence relative to the clinical incidence of neuroblastoma suggested that some of these tumors do regress, but the factors that determine whether the tumor would regress or continue to proliferate are unknown . In 1974 Turkel and Itabashi" examined adrenal glands from 92 fetuses from ten to thirty weeks' gestation . These authors found that all glands contained neuroblastic nodules, which they concluded were an integral part of the normal morphogenesis of the adrenal gland, and were not representative of malignant tumors . They noted that these nodules were most common in fetuses of seventeen to twenty weeks' gestation, and the largest were 200 to 400 t in diameter. In addition, the migrational pathway of the neuroblastic nodules was traced from the perivertebral sympathetic ganglia to the periadrenal sympathetic collections . These authors concluded that the neuroblastic nodules
UROLOGY
MARCH 1986 / VOLUME XXVII . NUMBER 3
increased to a certain maximal number and then coalesced or disappeared by early infancy . Unfortunately their study was not carried beyond thirty weeks' gestation . In 1979 Gibbons and Ducketts described a case of neuroblastoma which masqueraded as a UPJ obstruction at three days of age . However, by day 5 the abdominal mass had grown threefold, and the clinical impression changed from one of mild hydronephrosis to that of a flank tumor. Abdominal exploration demonstrated the mass to be an extra-adrenal neuroblastoma which had encased the kidney and ureter . Although we can only speculate on the biologic potential of this lesion, on the basis of the size of the ganglioneuroblastoma (1 .5 cm) in our patient aged eleven weeks, it seemed unlikely that this was a lesion that was about to regress spontaneously . The presence of ganglia, indicating some differentiation of the lesion, suggested a better prognosis for this particular form of neuroblastoma . In their histologic evaluation of 83 patients with neuroblastoma, Hughes, Marsden, and Palmere demonstrated a three-year crude survival rate of approximately 70 per cent of patients with mature ganglion cells in their tumor as opposed to less than 10 per cent in those patients with no evidence of differentiation within the neuroblastoma . Evans et al . in 19767 described the prognostic factors involved with localized neuroblastoma based on their series of 113 patients . Of 27 patients with fully resected Stage 1 disease (disease confined to the organ of origin), the authors noted no recurrences . In addition, they noted that survival was greater than 90 per cent in the first and second years of life and fell to 4 7 per cent if the child was older than two years of age . Of 55 children less than one year of age, 4 recurrences were noted . Evans found that the
UROLOGY
1
MARCH 1986
!
VOLUME
XXVII,
NUMBER
location of the primary tumor above or below the diaphragm was not significant with regard to tumor recurrence and that all patients who relapsed did so within one year . Goldman et al . in 19808 confirmed Evans' findings that stage and age of presentation were important prognostic indicators for neuroblastoma . In addition, they also found that there was improved prognosis if the primary neuroblastoma was of nonadrenal origin . It is uncertain that this incidentally discovered ganglioneuroblastoma would ever have become clinically manifest . However, according to the standard criteria for evaluating neuroblastoma including histologic differentiation, stage of disease, nonadrenal location of primary tumor and age of discovery, our patient's prognosis is a good one . University of Massachusetts Medical Center 55 Lake Avenue North Worcester, Massachusetts 01605 (DR. DIAMOND) References
Katz SE, and Schapira HE : Spontaneous regression of genitourinary cancer-an update, j Urol 128 : 1 (19821 . 2. Beckwith JB, and Perrin E V: In situ neuroblastomas : a contribution to the natural history of neural crest tumors, Am J Pathol 43: 1089 (1963) . 3 . Gum GH. Gilbert EF, and Jones B : Incidental neuroblastomas in infants, J Clin Pathol 51 : 126 (1969) . 4 . Market SB, and Itabashi HH : The natural history of neuroblastic cells in the fetal adrenal glands, Am J Pathol 76 : 25 1.
(1974) . 5 . Gibbons
MD, and Duckett JW : Neuroblastomas masquerading as congenital ureteropelvic junction obstruction, j Pediatr Surg 14 : 420 (1979) . 6 . Hughes M, Marsden MB . and Palmer MK : Histologic patterns of neuroblastoma related to prognosis and clinical staging, Cancer 34 : 1706 (1974) . 7 . Evans AE . et al : Factors influencing survival of children with nonmetastatic neuroblastoma, ibid 38 : 661 (1976) . 8 . Coldman AJ, Fryer CJH, Elwo od JM, and Sonlev MJ : Neurohlastoma influence of age at diagnosis, stage ., tumor site, and sex on prognosis, ibid 46 : 1996 (1980) .
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