Clinicopathologic Conference

Transcription

1 Participants: Mohammed Akhtar, MD*, Nabil Bissada, MD and William Cumming, MD Editor. John T. Godwin, MD, FCAP * Director, Electron Microscopy Section, Department of Pathology and Laboratory Medicine; Urologist, Department of Surgery; Radiologist, Department of Radiology; Chairman, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre M Akhtar, N Bissada, W Cumming, Clinicopathologic Conference. 1983; 3(2): Case Presentation A 2½-year-old Saudi male was admitted to King Faisal Specialist Hospital and Research Centre because of a right upper quadrant abdominal mass. The child was apparently doing well until about a month before admission when he had an episode of gross hematuria that lasted for about 24 hours. A local physician discovered a large abdominal mass in the upper quadrant and referred the patient for further evaluation. Both parents and siblings were apparently healthy. On physical examination the child was of normal height and weight for his age and was in no apparent distress. A mass measuring approximately 10 cm was palpated in the right flank. This was mobile and had a nodular surface. There was resonance on percussion over the mass. The remainder of the physical examination was unremarkable. No congenital anomalies were detected. Complete blood count and SMAC-20 blood chemistry were normal. Urinalysis revealed no albuminuria and no WBC or RBC in the urinary sediment. Plasma renin and urinary levels of vanillymandelic acid (VMA) and catecholamines were within normal limits. An outside intravenous urogram was reported as showing nonvisualization of the right kidney. An abdominal exploration was performed. The right kidney was enlarged and cystic. An S-shaped kink in the uppermost part of the ureter was found. The upper ureter and the renal pelvis were distended by a firm, smooth mass. The mass was sessile and seemed to be attached to the renal pelvis proximally. A right nephrectomy with ureterectomy was performed. Dr Nabil Bissada: The most common abdominal masses in infants and children include hydronephrosis, cystic renal disease, Wilms' tumor, neuroblastoma, splenomegaly, lymphoma, and hepatoma. About 40 percent of all masses in children are surgical and about half of these arise in the urinary tract. In infants, urinary origin is even more likely. 1-3 Here we are dealing with a 2½-year-old male child who has a mass involving the right kidney which seems to be nonfunctioning. The mass is described here as cystic. In addition there seems to be dilatation and obstruction of the renal pelvis and upper part of the ureter by another mass which is described as well circumscribed, fleshy and sessile. Several possibilities may be considered: a hydronephrotic kidney due to obstruction of the ureter and pelvis, Wilms' tumor involving the kidney and extending into the renal pelvis and ureter, a multicystic kidney (unilateral renal dysplasia) and some uncommon renal lesions such as congenital mesoblastic nephroma and a multilocular cyst of the kidney. At this point I would like to ask Dr Cumming to present the radiologic workup on this patient. Dr William Cumming: A right-sided abdominal mass in a 2½-year-old boy has several possible diagnoses, which have been mentioned by Dr Bissada. As the first step in diagnosing the organ or origin of the mass, ultrasonography provides a simple, safe and effective examination. It also tells whether the mass is cystic or solid. Figure 1 shows a large multicystic mass replacing the right kidney. This mass is apparently of renal origin and the mixture of solid and cystic components suggests two possible diagnoses: Wilms' tumor and multicystic dysplastic kidney. Hydronephrosis, neuroblastoma lymphoma, and hepatoma are all excluded. Wilms' tumors arise from the kidney, grow to considerable size, and are occasionally cystic. They rarely completely replace a kidney but may appear to do so on ultrasonography. The appearance of the mass, however, is more that of a multicystic dysplastic kidney than of a Wilms' tumor.

2 Figure 1. An abnormal ultrasonogram showing a multicystic mass behind and below the right lobe of the liver. A plain abdominal radiogram showed a soft tissue mass in the region of the right kidney. Excretory urography (IVP) (Figure 2) showed no excretion on the right side and a large functioning kidney on the left. The enlarged left kidney indicates compensatory hypertrophy and suggests that the right kidney has not functioned for a long time, if ever. This favors a diagnosis of multicystic dysplastic kidney rather than a Wilms' tumor, which would destroy renal function only after a long time and would be unlikely to result in hypertrophy of the contralateral kidney in a 2½year-old. Wilms' tumor metastasizes to the lung and liver where it can be seen with chest radiography and nuclear liver scanning. This patient's chest shows no sign of pulmonary metastases. A liver scan was not done but ultrasonography showed no sign of liver metastases. Very rarely, Wilms' tumors metastasize to bone and a bone scan done on this patient shows no sign of skeletal metastases. One examination that might have been helpful is the cystogram which often shows reflux into a club-shaped atretic ureter in a patient with multicystic dysplastic kidney. The finding is diagnostic of that condition. Figure 2. Excretory urogram showing a large left kidney and a mass apparently replacing the right kidney.

3 In summary, we have a multicystic mass that completely replaces one kidney. We have evidence that it has been there for a long time, possibly since before birth. These are the findings of a multicystic dysplastic kidney with a cystic Wilms' tumor as a less likely alternative. Dr Nabil Bissada: Differential Diagnosis It seems that clinical, operative, and radiologic findings in this case are those of a nonfunctioning kidney replaced by a cystic mass. Another well circumscribed, sessile mass is causing dilation and obstruction of the renal pelvis and the proximal ureter. A relatively common cause of nonfunctioning kidney in infants and children is the multicystic kidney. It is a form of renal dysplasia involving an entire kidney. A common associated finding is atresia of a portion of the ureter. Renal pelvis may be normally formed in patients with segmental dysplasia, although it is generally absent in those cases of multicystic kidney in which an entire kidney is involved. The condition is congenital but not familial. The contralateral kidney may be normal or may be involved. A variety of other congenital anomalies such as esophageal atresia, interventricular septal defects, and lumbosacral dystraphias may be associated with this condition. None of these was present in our patient. Demonstration of a nonfunctioning right kidney in this patient would imply that perhaps the entire kidney was involved by renal dysplasia. However, the presence of a normally formed renal pelvis and ureter is not compatible with a multicystic kidney. Moreover, the operative finding of a sessile mass in the renal pelvis and ureter is not explained by renal dysplasia. Furthermore, this patient had an episode of hematuria which is not a feature of renal dysplasia. I therefore feel that renal dysplasia is an unlikely diagnosis in this patient. Wilms' tumor is the most common renal neoplasm in infants and children. The tumor is usually well circumscribed and in a majority of cases involves only part of the kidney, although on occasion the entire kidney may be completely replaced by tumor. It is usually a solid tumor although areas of cystic degeneration may be present. Rarely, Wilms' tumor may be predominantly cystic. It is conceivable that this patient has a predominantly cystic Wilms' tumor that is replacing most of the renal parenchyma and is also extending into the renal pelvis. Hematuria is uncommon in patients with Wilms' tumor although it is more likely to occur in those cases in which the tumor extends to the collecting system. Other renal lesions that should be considered in this case include congenital mesoblastic nephroma, a multilocular cyst of the kidney and a primary tumor arising in the renal pelvis. Congenital mesoblastic nephroma is an uncommon renal tumor and it usually presents in infancy. It is considered to be hamartomatous maldevelopment rather than a true neoplasm. The clinical course is almost invariably benign, although in two cases reported in the literature the tumor recurred after resection. Cystic changes in congenital mesoblastic nephroma are rare and extension into the renal pelvis and ureter has not been reported. Hematuria is also not a feature of this lesion. It is therefore unlikely that this patient has a congenital mesoblastic nephroma. Another rare lesion that needs consideration is multilocular cyst of the kidney. This is a congenital condition that is always unilateral and may present clinically as an abdominal mass. The lesion involves only part of the kidney and is composed of a large number of cystic spaces. The lesion is benign and its neoplastic nature has not been fully established. A large majority of the lesions are limited to the renal parenchyma, although rarely herniation of one or more of the daughter cysts into the renal pelvis has been described. Thus it is possible that in our patient the kidney was involved by a multilocular cyst with herniation of the cysts into the renal pelvis. Again, hematuria is uncommon in association with multilocular cyst of the kidney but has been reported on several occasions. The possibility of a primary tumor arising in the renal pelvis and secondarily causing hydronephrosis of the kidney has been excluded by radiologic studies. Furthermore, primary tumors of the renal pelvis very rarely occur in the pediatric age group. Of all the possibilities mentioned earlier, it appears to me that there are two conditions that might explain the clinical, radiologic and operative findings in this patient. These are: (1) a cystic Wilms' tumor with extension of the tumor into the renal pelvis and ureter, or (2) multilocular cyst of the kidney with herniation of the daughter cysts into the renal pelvis. Dr Akhtar. Pathological Discussion The specimen consisted of a kidney measuring 11 x 6 x 4.5 cm. The upper half was replaced by a well-

4 circumscribed, encapsulated, multilocular cyst surrounded by compressed renal parenchyma. The locules of the cyst averaged 1 cm in diameter, contained clear fluid, and were separated from one another by fibrous septa. The lower half of the kidney showed a dilated renal pelvis. The calyces were surrounded by somewhat atrophic renal parenchyma which varied from 0.5 to 2 cm in thickness. The calyces and the pelvis, including the adjacent part of the ureter, were occupied by polypoid, fleshy, cystic masses measuring from 1 to 3 cm in diameter. These masses appeared to be an extension of the multiloculated cyst noted in the upper half of the kidney (Figure 3). Figure 3. Gross appearance of the nephrectomy specimen. Upper pole of the kidney is replaced by a multilocular cystic mass. In the lower half, dilated calyxes occupied by polypoid masses are seen. These are surrounded by atrophic renal cortex. Microscopically, the main renal mass consisted of numerous cystic spaces lined by low cuboidal to columnar epithelium (Figure 4). In some of these cysts, the lining epithelial cells showed varying degrees of proliferation but no significant atypia (Figure 5). The cysts were separated by fibrous septa that varied considerably in their thickness. The septa were mostly composed of loosely arranged spindle-shaped cells. In some areas, however, these septa were markedly thickened and contained closely packed bundles of these cells (Figures 5 and 6). In addition, within the fibrous septa occasional small clusters of undifferentiated cells resembling primitive renal tissue were seen (Figure 7). The morphology of the polypoid cystic mass within the renal pelvis was identical to that of the main mass (Figure 8). Sections from the apparently uninvolved renal parenchyma showed changes of chronic pyelonephritis (Figure 9). These features indicate that we are dealing with a multilocular cyst of the kidney. Figure 4. A low magnification photomicrograph of the multilocular cyst. Individual cysts are lined by cuboidal epithelium and are separated from one another by fibrous septa (H&E, x 150).

5 Figure 5. Higher magnification view of the cyst. The septa are moderately cellular and contain spindle-shaped eel, (H&E, x 200). Multilocular cyst of the kidney was first described by Edmunds in Since then, fewer than 100 cases have been reported. Of these, approximately half have been seen in infants and children. 5,6 The lesion presents as an abdominal mass, although occasionally hematuria may also be a presenting clinical feature. It is almost always unilateral. The pediatric patients range in age from neonates to 5 years. Adult patients range in age from 18 to 71 years. The reason for this peculiar age distribution is not clear. Powell and coworkers in 1951 suggested eight criteria for a pathologic diagnosis of multilocular cyst of the kidney. These were modified by Boggs and Kimmelsteil 4 (Table 1). Cases of multilocular cysts in infants and children can be divided into two subgroups. The first group includes multilocular cysts that are entirely composed of epithelial-lined locules separated by fibrous septa. Multilocular cysts in the second group in addition contain variable amounts of organoid embryonic tissue. The cysts in the first group are similar to those seen in adults. The cysts included in the second group, however, are unique to the pediatric group and have not been reported in adults. 5 The significance and the true nature of the embryonic tissue present in these cysts are not clear. Some authors have suggested that cysts containing these elements should not be categorized as multilocular cysts but should instead be called a cystic differentiated variant of nephroblastoma (Wilms' tumor). This has led to a variety of designations applied to this lesion (Table 2). An alternate interpretation would be that this tissue represents residual metanephrenic blastema. Nodules of metanephric blastema are occasionally seen as an incidental finding in normal kidneys of infants and children. Nephroblastomas presumably arise from some of these nodules; however, an overwhelming majority of these regress spontaneously. 7 Figure 6. Another area of the cyst featuring locules lined by hyperplastic epithelium. These are surrounded by uniform spindle-shaped cells (H&E, x250).

6 The follow-up data pertaining to the multilocular cysts indicate that these are benign lesions that are adequately treated by nephrectomy. It is also apparent that the prognosis of multilocular cysts is not adversely affected by the presence of primitive embryonic tissue. 5 This would further support the concept that the foci of embryonic tissue are not neoplastic and most probably undergo spontaneous regression in a manner similar to that seen in the nodules or metanephric blastema in normal kidneys of infants and children. This would explain why such foci have never been encountered in any of the multilocular cysts seen in the adults. An interesting and rare feature in our patient is the herniation of some of the daughter cysts from the main lesion into the renal pelvis. 4 This obstruction produced pyelonephritic changes in the remaining part of the kidney and explains why the right kidney was completely nonfunctioning even though the cyst involved only the upper pole. Final Pathologic Diagnosis: Multilocular cyst of the kidney with embryonic tissue. Herniation of daughter cysts into the pelvis and ureter. Chronic pyelonephritis of the remaining part of the kidney. Dr Mohammed Faysal. Discussion Is multilocular cyst of the kidney a neoplasm or a developmental anomaly such as renal dysplasia? Dr Akhtar. The exact nature and histogenesis of this lesion are still a matter of debate and controversy. Some authors believe it to be a form of segmental renal dysplasia; others have called it a cystadenoma, implying a benign tumor. In the pediatric age group, those multilocular cysts that have variable amounts of embryonic renal tissue have been interpreted by some as differentiated variants of Wilms' tumors implying a maturation of a Wilms' tumor into a multilocular cyst, analogous to the maturation of neuroblastoma to ganglioneuroma. 9 Figure 7. Photomicrograph from another area in the cystic mass.`clusters of undifferentiated cells resembling renal blastema are seen (arrows) (H&E. x 200).

7 Figure 8. Photomicrograph of the mass within the renal pelvis. It is composed of locules separated by fibrous septa (H&E, x 100). Figure 9. Photomicrograph showing a representative area from the apparently uninvolved part of the kidney. There is dilatation and atrophy of the renal tubules. Moderately dense infiltration of lymphocytic cells is present within the interstitium (H&E, x150). Table 1. Criteria for diagnosis of multilocular cyst of the kidney 1. The cyst should be unilateral.* 2. It should be solitary. 3. It should be multilocular. 4. The locules should not communicate with one another. 5. The locules should have an epithelial lining. 6. The cyst should not communicate with the pelvis. 7. The remaining kidney should be normal. 8. No fully developed nephrons or portions of nephrons should be present in the septa of the cystic lesion. *One case with bilateral multilocular cyst has now been reported. 8

8 Dr M. Ashraf Ali: Table 2. Synonyms used for multilocular cyst of kidney in the pediatric age group Benign multilocular cystic nephroma Renal cystadenoma Partial polycystic kidney Polycystic nephroblastoma Cystic nephroma Benign cystic differentiated nephroblastoma Well-differentiated nephroblastoma Well-differentiated polycystic Wilms' tumor Cystic partially differentiated nephroblastoma Differentiated nephroblastoma Could the exact diagnosis have been made preoperatively in this case? Dr Bissada: No. The diagnosis of a cystic renal mass was made here. However, a multilocular renal cyst usually presents as an expansile mass distorting the collecting structures. Although failure of contrast medium to be excreted has been mentioned in connection with herniation of daughter cysts into the pelvis, the association of a cystic renal mass with nonexcretion of contrast is much more likely to be due to a multicystic kidney or cystic Wilms' tumor. Dr Cumming: We were misled in this investigation by not learning that there was an intact right ureter or that some normal renal tissue was present on the right side. Either of these pieces of information would have excluded multicystic dysplastic kidney as a diagnosis. It is very unusual for a multilocular renal cyst to cause complete absence of renal function. This one apparently did it by occluding the renal pelvis. It would be an unusual Wilms' tumor that was present long enough to destroy the function of the kidney, causing compensatory hypertrophy of the other, without signs of malignancy. Therefore, learning of the presence of renal tissue with a nuclear scan or the presence of a normal ureter with a cystourethrogram should have caused us to think seriously of the probability of a multilocular cyst. These studies, however, were not performed in this case. Dr Akhtar: Dr Rajih Sabbah, chairman of the Department of Oncology, has considerable experience with abdominal tumors in children. I wonder if he has any comments in regard to this case. Dr Sabbah: Two questions need to be asked: could the diagnosis have been made preoperatively, and, if so, would that have changed the treatment? As indicated in the discussion, the only malignant condition that entered into the differential diagnosis was Wilms' tumor. This condition could have been ruled out preoperatively. The degree of multicystic changes, the nonfunctioning of the kidney, and the chronicity of the problem, as indicated by hypertrophy of the other kidney, make the possibility of Wilms' tumor unlikely. Fortunately, failure to reach a definite preoperative diagnosis did not adversely affect the management in this patient since nephrectomy would have been indicated anyway. However, as a general rule, it is always desirable to know whether or not a malignant condition exists before the patient is taken to the operating room. Dr Hernando Bunuan: How urgent is the need to operate on a child with a suspected abdominal tumor?

9 Dr Bissada: Two factors must be considered here. First, most childhood cancers grow rapidly and prolonged hospitalization may increase the chances of metastasis occurring. Therefore, undue loss of time should be avoided. On the other hand, the diagnostic and therapeutic approach to abdominal masses must be thoughtfully and carefully planned. Accordingly, adequate workup should be completed promptly. Most of the studies need to be completed within 48 hours of the patient's admission to the hospital. This allows the team of physicians caring for the patient to choose the best therapeutic approach. REFERENCES 1. Wedge JJ, Grosfeld JL, Smith JP: Abdominal masses in the newborn: 63 cases. J Urol 106: Lee SL: Childhood abdominal masses. J Singapore Paediatr Soc 14: Melicow MM, Unon AC: Palpable abdominal masses in infants and children: A report based on a review of 653 cases. J Urol 81: Aterman K, Boustani P, Gillis DA: Solitary multilocular cyst of the kidney. J Ped Surg 8 (4): Akhtar M, Qadeer A: Multilocular cyst of the kidney with embryonic tissue. Urology 16: Baldauf MC, Schulz DM: Multilocular cyst of the kidney. Report of three cases with review of literature. Am J Clin Pathol 65: Bove KE. McAdams AJ: The nephroblastomatosis complex and its relationship to Wilms' tumor: a clinicopathologic treatise. Perspect Pediatr Pathol 3: Chatten J, Bishop HC: Bilateral multilocular cysts of the kidneys. J Pediatr Surg 12(5): Fowler M: Differentiated nephroblastoma: solid, cystic or mixed. J Pathol 105: