| Abstract|| |
Multicystic nephroma (MCN) is an uncommon, non-heritable, unilateral, benign tumor that represents 2-3% of all primary renal tumors in the pediatric age group. It is characterized by bimodal age incidence with 50% of cases seen in children less than four years of age. Presented here is an 8-month-old boy with asymptomatic, gradually progressive renal lump of two months duration, with no other complaints. Ultrasound of the abdomen showed a well-defined multi-septated cystic mass involving whole of the kidney. Computerized Tomography (CT) scan revealed a unilateral cystic lesion involving almost the entire left kidney. Keeping in mind the age, clinical presentation and radiological appearance, the possibility of cystic variant of Wilms' tumor could not be ruled out pre-operatively. An elective left nephrectomy was done. The histopathological report revealed MCN of the left kidney. Only a few cases have been reported from India. We report here one such pediatric case.
|How to cite this article:|
Mehra BR, Thawait AP, Akther M, Narang RR. Multicystic nephroma masquerading as Wilms' tumor: A clinical diagnostic challenge. Saudi J Kidney Dis Transpl 2011;22:774-8
|How to cite this URL:|
Mehra BR, Thawait AP, Akther M, Narang RR. Multicystic nephroma masquerading as Wilms' tumor: A clinical diagnostic challenge. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Sep 21];22:774-8. Available from: http://www.sjkdt.org/text.asp?2011/22/4/774/82690
| Introduction|| |
Multicystic nephroma (MCN) is a renal tumor of uncertain origin. Boys usually predominate in the pediatric age group (2:1 ratio), whereas women predominate among adults. The tumor is bulky, well encapsulated, non-infiltrating and is composed of multiple non-communicating, fluid-filled locules. It is usually expansive and generally replaces a major part of the involved kidney. MCNs are commonly found incidentally on radiographic studies, but may present as an abdominal mass found on routine physical examination. The differential diagnosis of MCN includes cystic partially differentiated nephroblastoma (CPDN), Wilms' tumor with cystic change, multicystic dysplastic kidney, malignant necrotic and hemorrhagic masses (renal cell carcinoma) and cystic mesoblastic nephroma. MCN and CPDN/solid nephroblastoma (Wilms' tumor) represent benign and malignant ends of a spectrum, respectively; however, the exact relationship between these entities is not known and is rather controversial. Differentiation between these entities has a prognostic and diagnostic significance. MCN is the most differentiated form in the spectrum. To label a lesion as MCN, presence of blastemal cells and poorly differentiated cells should be ruled out. Since carcinomatous degeneration may occur within the wall of such tumors, surgery is the treatment of choice. The extent of surgery reported in literature for such cases has ranged from complete excision, partial nephrectomy to radical nephrectomy, as performed in our patient. Recurrence has occurred following incomplete excision by partial nephrectomy. If partial nephrectomy is considered, frozen section is indicated to exclude cystic partially differentiated nephroblastoma.
| Case Report|| |
An 8-month-old male child presented to the Department of Surgery with history of asymptomatic, gradually progressive lump in the left lumbar region of two months duration, discovered incidentally by his parents. The child had normal weight for age (8 kg), was taking feeds normally and had normal bowel movements. There was no history of fever or urinary complaints. Physical examination revealed a child of normal weight, fairly nourished with no pallor. On abdominal examination, a single lump was felt in the left lumbar region extending to the left hypochondriac and umbilical regions. The lump was approximately 10 cm × 8 cm in its maximum dimensions, had lobulated surface, ill-defined margins, soft consistency and cystic feel. The remaining part of the systemic examination was within normal limits. Keeping the possibility of Wilms' tumor, the child was further investigated.
Routine hemogram and biochemistry showed no abnormality. Urine routine, microscopy and cytology were also within normal limits. Plain X-ray of the chest and abdomen did not add to the diagnosis. Ultrasound of the abdomen showed a well-defined multiseptated cystic mass in the left lumbar region, measuring 14.8 × 9.1 × 6.4 cm. The left kidney could not be visualized separately from the mass. Intravenous urography revealed bilaterally normal functioning kidneys with radio opaque soft tissue density mass in the left renal region extending from T10 to L2 vertebra, displacing bowel loops toward the right side and causing splaying and displacement of the visualized left renal pelvis, lower calyx and proximal ureter, laterally. Computerized tomography (CT) scan of the abdomen showed a well-defined non-enhancing cystic mass lesion involving almost the entire left kidney with multiple enhancing thin internal septa, causing compression and stretching of the remaining enhancing renal parenchyma. Few cystic areas showed communication with each other. With a differential diagnosis of Multilocular Cystic Nephroma and cystic variant of Wilms' tumor, the child was surgically explored.
An elective left nephrectomy with partial ureterectomy was planned. Intra-operatively, no adhesions were found between the tumor and surrounding tissue. The excised kidney specimen measured 15 × 10 × 8 cm, weighed 650 g and was multinodular with partial cystic and partial solid component. The external surface showed congested blood vessels [Figure 1]. On cut opening, around 400 mL of fluid was drained. The cut surface was multiloculated with cystic areas having thin paper like walls and solid areas having gelatinous, myxoid, whitish appearance. The approximate size of the cystic lesion ranged from 1 to 3 mm. Normal appearing kidney was seen in one corner. Histopathologically, multiple cysts were seen with intervening fibroblastic stroma. The cysts were lined by tubular epithelium and were cuboidal to flat type, resembling endothelium [Figure 2]. It was reported as MCN. The child made an uneventful recovery, was discharged and is on regular follow-up.
|Figure 1: Photograph of the excised kidney specimen measuring 15 × 10 × 8 cm, showing multinodular surface with partial cystic and partial solid components. The external surface shows congested blood vessels.|
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|Figure 2: Microscopic appearance showing multiple cysts with intervening fibroblastic stroma. The cysts are lined by tubular epithelium and are cuboidal to flat type resembling endothelium.|
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| Discussion|| |
Cystic nephroma is a rare, non-heritable, unilateral benign renal neoplasm of uncertain cause that represents 2-3% of all primary renal tumors in the pediatric age group. The tumor was originally described by Edmunds in 1892 as a "cyst adenoma"  and since then, the spectrum of histologic findings and multiple theories of the pathogenesis of cystic nephroma have given rise to many synonymous terms, including benign multilocular cystic nephroma and cystic nephroblastoma. Cystic nephroma is now classified with CPDN as a multilocular cystic renal tumor. Cystic nephroma and CPDN are histologically distinct but anatomically and radiologically identical. In 1989, Joshi and Beckwith  proposed a modified terminology and refined the diagnostic criteria to help differentiate cystic nephroma from CPDN and other cystic renal tumors such as Wilms' tumor with cyst formation.
The prevalence of this non-familial condition is uncertain. Studies have confirmed a biphasic age and sex distribution: two-thirds of multi-locular cystic renal tumors occur in a predominantly male pediatric population between three months and two years of age; approximately one-third occurs in the female population, with a peak in the fifth and sixth decades of life.  There is no association with cysts in other organs and only sporadic association with other congenital anomalies.
Presenting symptoms vary with patient's age. Children typically present with a painless, progressively enlarging, palpable abdominal or flank mass that has a variable growth rate and may be discovered incidentally. Adults can present with a variety of nonspecific signs and symptoms, including abdominal and flank pain, urinary tract infection and hypertension. Hematuria, either microscopic or gross, can occur in either group.
Cystic nephroma demonstrates gross pathologic features that are indistinguishable from those of CPDN. Typically, it shows a well-circumscribed, non-infiltrating mass with a thick fibrous capsule containing multiple fluid-filled, non-communicating cystic spaces, separated by connective tissue septa. Generally, the mass is solitary, unilateral, and arises from the lower pole,  although occasionally (as in this case) it may almost completely replace the kidney. The mean size of the mass is usually 7.6 × 9.7 cm and the locules range from a few millimeters to 2.5 cm.  Calcification is rare. Necrosis and hemorrhage are uncommon but are usually seen in association with herniation of the tumor into the renal pelvis or ureter, which damages the thin layer of transitional epithelium. 
On microscopic analysis, the locules are lined by flattened cuboidal or slightly protruding epithelial cells. The fibrous septa lack the blastemal or other embryonal elements found in CPDN but may contain well-differentiated renal tubules. Adequate sampling is essential to distinguish between cystic nephroma and CPDN because the blastemal component theoretically portends the risk of development of Wilms' tumor. Local recurrence with CPDN was reported in a case of incomplete resection.  To our knowledge, however, there have been no reports of cystic nephroma demonstrating local aggressive behavior or malignant transformation. MCN is diagnosed by set of eight criteria as suggested by Powell et al in 1951.  These are (i) unilateral involvement (ii) solitary lesion (iii) multilocular nature (iv) non-communication of the cysts with one another (v) non-communication with the renal pelvis (vi) loculi lined by epithelium (vii) interlobular septa devoid of renal parenchyma (viii) normal residual renal tissue, if present. Two more criteria were added to distinguish multilocular cystic nephroma from cystic partially differentiated Wilms' tumor, namely, the tissue in the cyst must be entirely differentiated tissue and there must not be any blastematous or embryonal element.
Imaging is vital in differentiating cystic nephroma from other cystic renal masses such as Wilms' tumor with cyst formation, clear cell sarcoma, cystic variants of mesoblastic nephroma, and cystic renal cell carcinoma. Ultrasound and CT scan are the most commonly used imaging modalities in evaluating cystic nephroma and allow pre-operative diagnosis, appropriate surgical planning, and patient follow-up. In larger lesions, conventional abdominal radiography may demonstrate a soft-tissue mass with associated mass effect and displacement of bowel and adjacent structures. Calcification is infrequently seen; occasionally, however, ossification can occur within septa or within the renal capsule. Central or small peripheral curvilinear calcifications can occasionally be seen at the edge of the herniated pelvic portion. Banner et al reported one case of dense calcium rings in multiple cysts. 
On ultrasound, the renal origin of a cystic nephroma is confirmed by the claw or "beak" of normal-appearing renal parenchyma at the periphery of the mass, which displaces the collecting system and moves upon respiration. The size of the locules and the amount of stoma present determine the ultrasound appearance. Typically, there are multiple anechoic spaces separated by thin, echogenic septa with no solid elements. Ultrasound better delineates the internal architecture than does CT scan, especially if the septa are thin and do not enhance vigorously. Despite its cystic nature, cystic nephroma may appear as a complex, echogenic intrarenal mass due to small cysts causing multiple acoustic interfaces with the ultrasound beam. 
On CT scan, the locules are typically slightly hyper-attenuating relative to water. Small locules (<1 cm) or the presence of myxomatous material within the cysts and the close association with the fibrous septa may cause all or part of the mass to appear solid. The septa enhance moderately due to their vascularity; the enhancement is less than the septa in renal cell carcinoma.  Contrast material does not accumulate in the cysts because they do not communicate with the collecting system. As in this case, herniation of cysts into the renal pelvis and ureter is readily demonstrated on CT scan. Uson and Melicow  postulated that cysts herniate through a rent in the calyx created by stretching of the calyces due to a sudden increase in intra-abdominal pressure in the presence of a tough fibrous renal capsule.
Magnetic resonance (MR) imaging of cystic nephroma has been limited due to the rarity of this lesion and, as with our patient, the sufficiency of CT and ultrasound for characterizing the mass. Kettritz et al performed multisequential and multiplanar MR imaging in seven patients, and the results confirmed the presence of multilocular cystic renal tumors. The capsule and septa have low signal intensity on T2-weighted MR images, a finding that reflects the presence of fibrotic elements.  Locules have varying signal intensity depending on the protein or blood product content. Thin internal septa typically enhance after gadolinium administration. Herniation into the renal collecting system was confirmed in all patients in the Kettritz series. 
Renal scintigraphy has also played a limited role in the diagnosis of cystic nephroma. Occasionally, faint radiotracer activity may be seen suggesting uptake of technetium-99m diethylenetriaminepentaacetic acid by the septa.
Many diverse disease processes may result in a multi-loculated renal mass, including cystic neoplasms, unilateral autosomal dominant polycystic kidney disease, and localized cystic disease of the kidney. Any solid childhood renal neoplasm may undergo hemorrhage and necrosis and look like a multi-locular cystic renal tumor. The presence of solid elements (blastema) excludes cystic nephroma and implies a more aggressive neoplasm. Cyst formation occurs in less than 10% of Wilms' tumors, and rarely is the growth pattern predominantly cystic. Cystic nephroma can be differentiated from Wilms' tumor by the absence of expansile solid masses of nephroblastomatous tissue. To our knowledge, cystic nephroma has not been diagnosed antenatally and does not occur in the neonatal period, observations that help distinguish it from clear cell sarcoma and cystic variants of mesoblastic nephroma. Multi-cystic dysplastic kidney (MCDK) can be differentiated from cystic nephroma by the absence of normally functioning renal parenchyma and by symmetric contrast material excretion on CT by the remaining normally functioning parenchyma in patients in whom a large portion of the kidney has been replaced by cystic nephroma. In MCDK, it is possible to observe an enhancing central core of solid dysplastic tissue, but this enhancement is different from that of normal renal parenchyma. Segmental MCDK may occur in the obstructed moiety (typically the upper pole moiety) in patients with complete ureteral duplication. At imaging, it may be possible to distinguish segmental MCDK from cystic nephroma without evidence of complete duplication.
Treatment of cystic nephroma consists of surgical excision, which is curative; either nephrectomy or nephron-sparing surgery with tumor-free margins is performed. In our case, the patient had an uneventful recovery after undergoing complete resection of the cystic nephroma.
In conclusion, MCN of kidney is a benign condition that carries an excellent prognosis. If the pathologist can make a pre-operative diagnosis with certainty, then the surgeon can offer the patient conservative surgery to preserve as much kidney as possible. However, in most of the cases, surgery precedes the diagnosis, which can only be made with certainty by histological examination of the resected specimen.
| References|| |
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Bhupendra R Mehra
Type II, Quarter No. 8, Kasturba Health Society Campus, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra
[Figure 1], [Figure 2]