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ORIGINAL ARTICLE
Year : 2018  |  Volume : 23  |  Issue : 1  |  Page : 22-26
 

Multiloculated cystic renal tumors of childhood: Has the final word been spoken


1 Department of Paediatric Surgery, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Web Publication27-Dec-2017

Correspondence Address:
Jujju Jacob Kurian
Department of Paediatric Surgery, Christian Medical College, Vellore, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaps.JIAPS_224_16

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   Abstract 


Background: Multicystic renal tumors which include cystic nephroma, cystic partially differentiated nephroblastoma (CPDN) and cystic Wilms tumor has been a diagnostic and therapeutic challenge. Histopathological examination has been the only reliable differentiating method. Management of these tumors is still riddled with controversy as a definitive preoperative differentiation between the three has not been possible.
Methods: A retrospective evaluation was performed of the treatment strategies employed with nine cases of multicystic renal tumors treated from 2005 to 2015.
Results: The median age at presentation was 12 months with all except one being boys. All except two children underwent primary surgery. The median follow-up was 50 months with six children having long-term survival. One child succumbed to the disease process, one died due to an unrelated cause and another was lost to follow-up. Although there was no ambiguity with cases of cystic nephroma (CN) and cystic Wilms tumor, three of the four cases of CPDN had problems.
Conclusion: Primary surgery for multicystic renal tumors is safe and should be seriously considered as it prevents overtreatment in cases of CN and early stage CPDN. Further studies are needed to fully understand the biological behavior of CPDN.


Keywords: Cystic nephroma, cystic partially differentiated nephroblastoma, cystic Wilms tumor, multicystic renal tumors


How to cite this article:
Kurian JJ, Jehangir S, Korula A. Multiloculated cystic renal tumors of childhood: Has the final word been spoken. J Indian Assoc Pediatr Surg 2018;23:22-6

How to cite this URL:
Kurian JJ, Jehangir S, Korula A. Multiloculated cystic renal tumors of childhood: Has the final word been spoken. J Indian Assoc Pediatr Surg [serial online] 2018 [cited 2019 Sep 20];23:22-6. Available from: http://www.jiaps.com/text.asp?2018/23/1/22/221596





   Introduction Top


The gamut of multiloculated cystic renal tumors (MCRTs) in children includes cystic nephroma (CN), cystic partially differentiated nephroblastoma (CPDN) and cystic Wilms tumor (CWT). CPDN occupies an intermediate position between the benign nephroma and malignant Wilms tumor. Although the tumors are histologically distinct, they are clinically indistinguishable. CWT has solid components which can be recognized on imaging; however, it is difficult to differentiate whether the solid component is part of the tumor or part of normal surrounding kidney. The therapeutic dilemma is further elaborated by the inability to take a core cut biopsy in cystic masses, the difficulty of reporting an isolated section if a biopsy is done and recommendations of the International Society of Pediatric Oncology (SIOP) where surgery alone is the therapeutic choice for CN, CPDN, and preoperative chemotherapy is advised for CWT. Here, we review 9 children with MCRT and describe the nuances which further highlight the diagnostic and therapeutic dilemma surrounding these tumors.


   Methods Top


An observational cohort study was conducted of children with multi loculated cystic renal tumors (MCRTs) who underwent treatment in the Department of Pediatric Surgery from 2005 to 2015. The nine patients (CN [n = 1], CPDN [n = 4] and CWT [n = 4]) were identified by an electronic search of Pediatric Surgery database of 119 renal tumors treated during the same period. The hospital outpatient records, operation notes, imaging, pathology reports, and discharge summaries were reviewed. Based on hospital data, the family was contacted by phone or followed up in the outpatient department. All management decisions were made at a multidisciplinary tumor board including pediatric surgeons, pediatric oncologists, and radiation oncologists.


   Results Top


Patients

MCRT comprised 7.6% of the total number of pediatric renal tumors. The children presented at a median age of 12 months (range 4 months to 180 months). There were eight boys and one girl. Six (78%) tumors were on the right, one (11%) on the left, and two (22%) were bilateral. Seven (78%) children presented with a palpable mass. Two children with CWT presented with fever. One child with CPDN had dysuria-hematuria and two were detected to be hypertensive during treatment. The comparative demographic details of the three tumor groups are described in [Table 1].
Table 1: The comparative demographic details of the three tumor groups

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Preoperative status

Preoperatively, the children were imaged with an ultrasonogram or a computerized tomogram (CT). The tumor volume was estimated using the ellipsoid formula (width [cm] × depth [cm] × length [cm] × 0.523 = volume [ml]). The average tumor volume was 366 ml (range 13.6–819 ml). The average tumor volume of CWT (230 ml) was almost half that of the benign counterparts (CN 405 ml and CPDN 541 ml). A CT-guided core biopsy was done in two of nine children. One was reported as CWT with rhabdomyomatous differentiation and the other CPDN. The final diagnosis in both children was CPDN.

Two children were given neo-adjuvant chemotherapy. Case 2, an 18-month-old girl who had a multiloculated cystic mass with solid areas within, which a core biopsy reported as CWT. Surgical excision done after six cycles of neoadjuvant chemotherapy revealed it to be CPDN. Case 4 was a 3-year-old boy who presented with a massive right multiloculated cystic lesion with solid areas within it. He was given three cycles of chemotherapy on the presumption of it being CWT. The tumor increased in size on chemotherapy causing respiratory distress. He underwent a right nephroureterectomy with positive margins. The final histopathology, however, was reported as CPDN.

Surgery

Six of seven children with unilateral involvement underwent an ipsilateral nephrectomy. One child with a unilateral CWT and two children with bilateral tumors had nephron-sparing surgery (NSS). There was no tumor spillage and margins were negative (Stage 1) in all except 1 child.

Outcomes and follow-up

The median follow-up was 50 months (range 2–66 months). Case 4, as described above with Stage 3 disease was further given adjuvant chemotherapy. Five months later, while on chemotherapy, he presented with breathlessness and was found to have a recurrence in the right renal fossa extending into the right chest and occupying the entire right hemithorax [Figure 1]. He was given second-line chemotherapy with cyclophosphamide and doxorubicin with which the tumor seemed to slightly regress. He was lost to follow-up 2 months later and was presumed deceased.
Figure 1: The CT scan of Case 4 which developed extensive recurrence

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Case 3, a 9 month old boy underwent bilateral NSS for CPDN. At 6 months follow-up, he was found to have bilateral recurrence. Excision biopsy revealed bilateral CWT. He was given 18 cycles of vincristine and actinomycin D to which he responded well. He died of unrelated causes at 2½ years of age.[1] There was only 1 child with CN (Case 1) who had bilateral disease and developed embryonal rhabdomyosarcoma of the anterior urethra 2 years after bilateral NSS. He completed treatment for the same and is well 60 months after the initial surgery.[2] One child with CWT was lost to follow-up after two cycles of chemotherapy. The details of surgery, chemotherapy and follow-up are summarized in [Table 2].
Table 2: Treatment and outcome of all multi loculated cystic renal tumors

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   Discussion Top


In the spectrum of pediatric multilocular cystic renal neoplasms, CN could represent the final stage of maturation of CPDN and CWT. A common origin for all three has been mooted from intralobar nephrogenic rests, which leads to a further question of whether there is a common pathway for tumor occurrence.[3]

Joshi and Beckwith in 1989 proposed clear histological criteria for differentiating MCRTs. A discrete mass composed of cysts lined by flattened, cuboidal, or hobnail epithelia and the intervening septa composed of fibrous tissue that may or may not contain well-differentiated tubules was designated as CN. The term CPDN was given for those lesions that contained poorly differentiated or blastemal elements within the septa.[4] The presence of solid components within a similar cyst with epithelial, stromal and/or mesenchymal elements was diagnostic of CWT.

The incidence of CN and CPDN according to SIOP and National Wilms tumor study group (NWTS) is around 0.56% and 0.5%, respectively.[5] A higher incidence of 4%, in the 10 years included in our study is inexplicable. A lack of other studies from the same area precludes a comparison in a similar genetic locale. Clinical differentiation is difficult as all three usually present with an abdominal mass, occasional hematuria and fever. CN and CPDN present in children <2 years while CWT has a peak age of occurrence of 3–4 years.[6] In our series, while three of the five children with CN and CPDN were <2, all four children with CWT were 18 months or less. Radiological imaging though helpful in diagnosing an MCRT is not useful in differentiating between the three. The only definite method of diagnosing the type of tumor is by histopathology. CN and CPDN were initially thought to have a bimodal age distribution with occurrence in childhood and adults.[7] However, recent evidence has shown the adult entity to be a distinct neoplasm which is now renamed as mixed epithelial and stromal tumor of the kidney.[8]

Although the histological classification is quite clear, there is a diagnostic and therapeutic dilemma. As demonstrated by Case 2 in this study, the radiological distinction of whether the solid component is part of the tumor or part of normal surrounding kidney is difficult. Further, a core biopsy may be misrepresented in the light of the presence of solid elements radiologically since immature elements may be seen in CPDN and CWT. The child was given preoperative chemotherapy according to the SIOP protocol. Chemotherapy was deferred postoperatively when she was diagnosed as Stage 1 CPDN on the surgical specimen. She is well 66 months later. However, diagnosing CPDN after neoadjuvant chemotherapy can be fallacious as it can obliterate a small solid component of tumor that would initially have led to a diagnosis of CWT.

The dilemma deepens as we explore Case 4. The tumor was unresponsive to neoadjuvant chemotherapy. He had gross residual tumor postsurgery and developed extensive local recurrence on first-line chemotherapy which further seemed to respond to second-line chemotherapy. This case was an enigma for us as the tumor behaved in a way that was too aggressive for a CPDN and CWT. A literature search revealed a case reported by Madewell et al. in 1983 where a similar disease progression and outcome occurred in an adult with multilocular CN with sarcomatous elements on histology.[9] In view of this, the blocks and slides of this child were reviewed by a senior pathologist and found to be consistent with CPDN [Figure 2] and [Figure 3]. The mystery of this child's clinical behavior still remains unsolved.
Figure 2: Cystic partially differentiated nephroblastoma with mesenchymal spindle cell stroma (H and E, ×40)

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Figure 3: Cystic partially differentiated nephroblastoma with cysts lined by flattened cuboidal cells and immature tubules with occasional blastemal cells (H and E, ×100)

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Wilms tumor has been described to occur alongside CN/CPDN in the same or the contralateral kidney.[10] Case 3, a child had bilateral CPDN recurred as bilateral CWT. There are 3 documented cases of recurrence with CPDN in the literature [Table 3].[1],[4],[11] This reiterates the caution by Joshi and Beckwith that the presence of poorly differentiated tissue and blastemal elements suggests possible malignant potential. In the cases where the histology was available, the recurrence was Wilms tumor. This correlation is very unlikely to be a casual coincidence and represents a progression toward the malignant spectrum.
Table 3: Summary of cases of recurrent cystic partially differentiated nephroblastoma

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The NWTS protocol mandates primary surgery for multilocular cystic renal neoplasms. While the indications for adjuvant treatment for CWT and CN are well defined, the need for the same in CPDN is dependent on the stage of the disease as elicited by Blakely et al.[12] They reviewed the outcomes of 21 patients with CPDN, of whom 13 received chemotherapy and 8 did not. As there was no difference in outcomes, the authors concluded that Stage 1 tumors had a 100% survival rate with tumor nephrectomy alone. In Stage 2 tumors, a nephrectomy followed by postoperative vincristine and dactinomycin chemotherapy resulted in excellent outcomes thereby suggesting that postoperative chemotherapy is useful for higher stage CPDN.[12]

The SIOP protocol recommends CN and CPDN be treated primarily by surgery, and CWT by a combination of neoadjuvant chemotherapy and surgery. However, as illustrated earlier the preoperative distinction is fallacious. This being the case we have reverted to performing a primary tumor excision for all MCRT even though the risk of intraoperative tumor rupture and tumor upstaging is significant.


   Conclusion Top


The subtypes of multicystic renal tumors can be differentiated only by histopathology. Upfront surgery is safe and can be undertaken for multilocular cystic lesions of the kidney. Complete tumor excision with no spill is of paramount importance. Although there is no ambiguity in the management of CN and CWT, CPDN still has some gray areas. The biological behavior of CPDN is still unclear, and concerted efforts to study this are required.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kurian JJ, Ninan PJ. A rare case of bilateral cystic partially differentiated nephroblastoma recurring as bilateral cystic Wilms tumour. BMJ Case Rep 2015;2015. pii: Bcr2015209771.  Back to cited text no. 1
    
2.
Kurian JJ, Sen S, Joseph RT, Bindra MS. A rare case of bilateral cystic nephroma associated with embryonal rhabdomyosarcoma of the penile urethra. J Indian Assoc Pediatr Surg 2015;20:82-3.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
van den Hoek J, de Krijger R, van de Ven K, Lequin M, van den Heuvel-Eibrink MM. Cystic nephroma, cystic partially differentiated nephroblastoma and cystic Wilms' tumor in children: A spectrum with therapeutic dilemmas. Urol Int 2009;82:65-70.  Back to cited text no. 3
[PUBMED]    
4.
Joshi VV, Beckwith JB. Multilocular cyst of the kidney (cystic nephroma) and cystic, partially differentiated nephroblastoma. Terminology and criteria for diagnosis. Cancer 1989;64:466-79.  Back to cited text no. 4
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5.
Luithle T, Szavay P, Furtwängler R, Graf N, Fuchs J; SIOP/GPOH Study Group. Treatment of cystic nephroma and cystic partially differentiated nephroblastoma – A report from the SIOP/GPOH study group. J Urol 2007;177:294-6.  Back to cited text no. 5
    
6.
Eble JN, Bonsib SM. Extensively cystic renal neoplasms: Cystic nephroma, cystic partially differentiated nephroblastoma, multilocular cystic renal cell carcinoma, and cystic hamartoma of renal pelvis. Semin Diagn Pathol 1998;15:2-20.  Back to cited text no. 6
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7.
Lowe LH, Isuani BH, Heller RM, Stein SM, Johnson JE, Navarro OM, et al. Pediatric renal masses: Wilms tumor and beyond. Radiographics 2000;20:1585-603.  Back to cited text no. 7
[PUBMED]    
8.
Silver IM, Boag AH, Soboleski DA. Best cases from the AFIP: Multilocular cystic renal tumor: Cystic nephroma. Radiographics 2008;28:1221-5.  Back to cited text no. 8
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9.
Madewell JE, Goldman SM, Davis CJ Jr., Hartman DS, Feigin DS, Lichtenstein JE. Multilocular cystic nephroma: A radiographic-pathologic correlation of 58 patients. Radiology 1983;146:309-21.  Back to cited text no. 9
    
10.
Vujanic GM, Jenney ME, Adams H, Meyrick SM. Juxtaposed cystic nephroma and Wilms' tumor. Pediatr Dev Pathol 2000;3:91-4.  Back to cited text no. 10
[PUBMED]    
11.
Baker JM, Viero S, Kim PC, Grant RM. Stage III cystic partially differentiated nephroblastoma recurring after nephrectomy and chemotherapy. Pediatr Blood Cancer 2008;50:129-31.  Back to cited text no. 11
[PUBMED]    
12.
Blakely ML, Shamberger RC, Norkool P, Beckwith JB, Green DM, Ritchey ML; National Wilms' Tumor Study Group. Outcome of children with cystic partially differentiated nephroblastoma treated with or without chemotherapy. J Pediatr Surg 2003;38:897-900.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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