Benign Renal Tumors in Pediatric Age Group: Retrospective Analysis.

BACKGROUND: Benign renal tumors are extremely rare and were studied here. This series also includes a renal teratoma in a horseshoe kidney, probably only the second in the pediatric literature.
MATERIALS AND METHODS: Retrospective review of children with benign renal tumors operated between 2006 and 2018 at one center.
RESULTS: Twelve patients (M:F ratio 10:2), age range 3 weeks (31-week gestation) to 13 years presented with large palpable renal swelling (n = 12) and hematuria (n = 3). Computed tomography (CT) scan showed features typical of the tumor. Final histopathology (age group [mean]) showed: multilocular cystic nephroma (MLCN) - n = 5 (41.7%), (11-16 months [13.6]); congenital mesoblastic nephroma (CMN) - n = 4 (33.3%) (classic 1, cellular 3) (0.75-5 months [2.125]); mature cystic teratoma - n = 1 (8.3%): (48 months, in a horseshoe kidney), and angiomyolipoma (AML) - n = 2 (16.7%) (144 months [sporadic] and 156 months [tuberous sclerosis]) One patient with cystic teratoma with no calcification on CT scan received pre-operative chemotherapy as fine-needle aspiration cytology (FNAC) reported malignant small blue cell tumor. Nephroureterectomy with Gerota's fascia could be done easily in all without intraoperative complications. Delay in presentation in MLCN and CMN led to increased symptoms and CT scan changes. All patients did well in 1.5-12 years (median 3 years) follow-up including cellular mesoblastic nephroma.
CONCLUSIONS: Benign renal tumors often occur in specific age groups but may overlap that of Wilms tumor. Proper interpretation of clinical presentation, CT scan, and FNAC findings help in avoiding preoperative chemotherapy. Upfront nephroureterectomy is curative. Histopathological findings decide further treatment. Children with AML and tuberous sclerosis need lifelong follow-up. Copyright:

INTRODUCTION

Renal tumors constitute 7% of all childhood tumors. More than 90% are Wilms' tumor (WT) with an incidence of 8.2 cases per 1 million children <15 years of age.[1] Non-Wilms malignant renal tumors include clear cell sarcoma of the kidney (CCSK), rhabdoid tumors, and renal cell carcinoma. Benign tumors of the kidney, due to their rarity, are likely to be misdiagnosed as WT and may receive unnecessary preoperative chemotherapy.[2] In this series, the benign renal tumors managed by the authors over a period of 13 years were analyzed, including the challenges faced during diagnosis and outcome after surgery.

MATERIALS AND METHODS

This was a retrospective review of all the cases of benign renal tumors in children from the neonatal period up to 15 years of age that were surgically managed in a single unit of a tertiary care pediatric surgery center from 2006 to 2018. The cases were operated by two senior pediatric surgeons with several years of surgical experience. Approval was obtained from the Institute Ethics Committee (NK/5948/Study/080) to publish retrospectively collected data and waiver for the consent of patients to participate in the study. The patient identifiers in images have been obscured.

Cases were initially evaluated on the basis of history and clinical examination. Baseline blood investigations such as hemogram, urea and creatinine were performed in all cases. Radiological diagnosis was initially by ultrasonography of kidney, ureter, bladder (USG KUB) region followed by contrast enhanced computed tomography (CECT) scan of the abdomen in all patients. Fine-needle aspiration cytology (FNAC) was performed where there was suspicion of WT based on clinical features or interpretation of CECT abdomen. CECT chest was performed only in those cases where imaging and FNAC suggested WT.

Patients underwent radical nephroureterectomy with Gerota's fascia with the removal of the entire ureter until just above the vesicoureteric junction. Wherever there was pre-operative suspicion of WT or nodes were prominent, lymph node sampling was done during surgery and areas documented. Intra-operative findings, which were noted were ease of removal of kidney, infiltration or adherence to local structures, rupture, uncontrolled bleed, vascular injury, hypotension requiring inotropic support, pneumothorax, etc. The immediate postoperative course of the patients was noted from admission files. The excised specimen was sent for histopathological examination (HPE), which was taken as the final confirmation of the benign nature of the disease and inclusion in the study group. Therefore, patients who received pre-operative chemotherapy based on clinical interpretation, CECT, and FNAC but were found to have benign renal tumor on HPE were also included. All malignant renal tumors were excluded. All histopathology slides were reviewed. Follow-up information was collated from data maintained in the outpatients.

RESULTS

A total of 12 patients were identified in the 13-year study period. There was a male predominance (M:F ratio; 10:2). The mean age was 35.38 ± 8.48 months (0.75–156 months). Based on nephrectomy HPE, the benign renal tumors encountered were multilocular cystic nephroma (MLCN) in 5 (41.7%); congenital mesoblastic nephroma (CMN) in 4 (33.3%); teratoma (mature cystic) in 1 (8.3%) and angiomyolipoma (AML) in 2 (16.7%). The images of each patient are placed in the same order as in Table 1 with figures of children with MLCN, CMN, Teratoma and AML given as Figures 1–4, respectively. The intra-operative pictures of one child with MLCN (S.No. 4) could not be traced.

Table 1

Details of study patients with benign renal tumor

Serial number	Age at surgery (months)	Weight (kg)	Sex	Side	Clinical presentation	CECT abdomen (size: AP × TR × CC, all in cm)	Operative findings	HPE	Figure number
1	11	10	Male	Right	Progressively increasing abdominal swelling, × 2 weeksHematuria, once, 1 month back	Well defined, (12×10×10), multilocular cystic lesion with contrast enhancement of septa and enhancing rim of compressed renal parenchyma sparing part of the lower pole which has normal contrast excretion. No area of necrosis or calcification or loss of fat planes. Lesion reaching into the renal pelvis; possibility of invasion cannot be ruled out	Globular cystic renal mass. Cysts contain clear fluid except one showing hemorrhage	MLCN	1 (a, b)
2	11	10.4	Male	Left	Incidentally detected swelling × 1 month	Fluid density mass lesion (8.6×8.2×8) in upper two-third of enlarged kidney. Rim shows contrast enhancement with large central nonenhancing fluid component with no solid component/calcification. Multiple thin internal septations within the mass show contrast enhancement. Residual kidney is displaced posteriorly and shows normal contrast excretion. Mass is reaching up to the anterior abdominal wall and displacing gut loops and pancreas to the right	Easy dissection with no adherence to other structures	MLCN	1 (c, d)
3	15	10	Male	Left	Incidentally detected swelling × 1 month	Well defined, (10×8×8) multiseptated cystic mass lesion arising from lower part of kidney and sparing upper pole with enhancing rim of compressed renal parenchyma (pseudocapsule). The mass shows cystic spaces of fluid attenuation value and multiple thick hyperdense internal septations. No significant solid element or calcification. The left renal collecting system is distorted by the mass. Left renal vein is clear of tumor invasion	Lower pole adherent to colon over 2 cm area. Cyst fluid hemorrhagic, yellow	MLCN	1 (e, f, g)
4	15	10	Male	Left	Weight loss × 2 monthso/e Palpable swelling	Well defined, (10×7×8) multilocular cystic lesion with contrast enhancement of thin septa and reaching abdominal wall maintaining fat planes. Residual lower pole kidney is displaced medially and anteriorly and shows normal contrast excretion	Easy dissection	MLCN	1 (h, i)
5	16	7.8	Male	Right	Progressively increasing abdominal distension/swelling × 11 monthsPain abdomen × 1 month	Large, multicystic, (14.5×13×10.7) retroperitoneal mass extending from subhepatic region (with indistinct fat planes with adjacent liver) and inferiorly reaching L5 level. The lesion has multiple septae with vessels traversing them. No fat/calcification/solid enhancing soft tissue in the mass. Right kidney is not visualized. Lesion is extending across midline and displacing bowel, mesenteric vasculature, pancreas to the left. Infrahepatic IVC not visualized and appears compressed by the mass	No local adherence, cysts contain clear fluid	MLCN	1 (j, k, l, m)
6	0.75	1.7	Male	Left	Incidentally detected swelling at birthPreterm birth at 31 weeks	Large, well capsulated, intrarenal, heterogeneously enhancing mass lesion (5.7×4.9×4.9) with post contrast enhancement up to 110 HU with multiple necrotic areas within, arising from midpole with positive claw sign, surrounding hypodense crescent shape width (14 mm maximum) no calcification, and displacing remaining kidney inferomedially not crossing midline, not encasing great vessels	Hard globular tumor, very vascular capsule, adherent to desc colon, mesocolon, DJ flexure, adrenal, pancreas, significantly enlarged draining vessels, significant lymphatics around narrow renal artery	Cellular CMN	2 (a, b, c)
7	0.75	2.4	Female	Right	Palpable swelling since birthAND at 36 weeks 5.5 cm × 4.3 cm lesion in right renal fossa with polyhydramnios	Well-defined, heterogenously enhancing exophytic (6.1×4.5×5.7) lesion arising from mid and lower pole of kidney compressing residual renal parenchyma to periphery along medial aspect, with loss of fat plane with psoas posteriorly, inferiorly extending till L5 level, no fat/calcification, not crossing midline	Globular enlarged, hard kidneyEasy dissectionNo nodes	Invasive cellular CMN	2 (d, e, f)
8	2	3.2	Male	Left	Incidentally detected swelling × 1 monthPreterm 36 weeks	Enlarged kidney with heterogeneously enhancing (7×6.3×6.7) mass lesion arising from mid and lower pole of kidney, with areas of necrosis, normal contrast uptake in upper pole with surrounding hypodense crescent-shaped width and multiple specks of calcification	Enlarged, hard kidneyEasy dissection	Classic CMN Focal cartilage formation	2 (g, h, i)
9	5	6	Male	Right	Progressively increasing abdominal swelling × 2 months	Heterogeneous (15×11×12) mass lesion involving entire kidney displacing liver anteriorly and aorta posteriorly, with lobulations having central areas suspicious of necrosis, crossing midline with no calcification. Retroperitoneal lymphadenopathy + (on Doppler, right renal vein displaced with no thrombus, normal patent suprarenal inferior vena cava)	Multilobulated renal swelling, covered by a thin transparent membrane, each lobule 2–6 cm in size, no infiltration, retroperitoneal nodes present, renal and gonadal veins are very prominent	Cellular CMN	2 (j, k, l)
10	48	15	Male	Right	Incidental diagnosis of abdominal swelling during investigation for nocturnal enuresisRight side hydrocephalus	Horseshoe kidney configuration with isthmus at level of L4 vertebra. Well defined peripherally enhancing (8.2×9×9) cystic lesion, likely to be arising from isthmus with mass effect and displacement causing pelvicalyceal system dilatation and cortical thinning (6 mm at midpole). A soft-tissue nodule (80 HU) is seen at left lateral wall and fatty attenuation area (70–80 HU) in anterior wall of mass with no calcification	Tumor arising from mid and lower pole of right half of horseshoe kidney with no plane of differentiation with upper pole of kidney or pelvicalyceal system	Mature cystic teratoma	3 (a – e)
11	156	50	Male	Left	Abdominal mass progressively increasing × 6 weeks Pain abdomenHematuria, once Tuberous sclerosis features +	Heterogeneous (30×24×23) mass with well-defined solid enhancing areas and nonenhancing cystic areas with necrotic components, no areas of fat attenuation, calcification. Replacing renal parenchyma except upper pole. Crossing midline but not encasing vessels	Large renal swelling reaching opposite flank with variable consistency and dilated veins over surface, adherent to colonic mesentery in a few places. Prominent renal vein with no thrombus	AML	4 (a - e)
12	144	36	Female	Left	Abdominal swelling × 2 monthsPain abdomen on physical activityHematuria, twice	Heterogenous (9 x 7 x 8) mass with solid enhancing and necrotic areas growing exophytically from interpolar region and lower pole, extending upto abdominal wall with no infiltration of surrounding structures	No adherence to surrounding structures	AML	4 (f, g)

AML: Angiomyolipoma, AND: Antenatal diagnosis, AP × TR × CC: Anteroposterior × transverse × cranio caudal, CECT: Contrast enhanced computed tomography, CMN: Congenital mesoblastic nephroma, DJ: Duodenojejunal, HPE: Histopathological examination, MLCN: Multilocular cystic nephroma, MRI: Magnetic resonance imaging, SMV: Superior mesenteric vein, TSC: Tuberous sclerosis complex, USG: Ultrasonography, IVC: Inferior vena cava

Figure 1

Images of Multilocular cystic nephroma patients: Computed tomography scans (a, c, e, f, h, i, j and k), gross specimen and cut sections (b, d, g, l and m) and histopathology slides (n). (I) Low magnification depicting multiple variably sized cysts (H and E, x100); (II) Fibrous septa dividing cysts and lacking immature nephrogenic elements, (H and E, x200); (III) High magnification showing low cuboidal cells forming the cystic lining (H and E x400)

Figure 4

Images of Angiomyolipoma patients: abdominal swelling crossing midline (a), Computed tomography scans (b and f), Magnetic Resonance Imaging brain (c), tuberous sclerosis skin lesions (d), specimen/cut section (e and g), Histopathology (h). (I) Low magnification showing triphasic elements composed of myoid spindle cells, mature adipose tissue and dysmorphic thick walled blood vessels; (II) High magnification depicting vascular component is in the form of thick walled hyalinized blood vessels without elastic lamina (H and E x400); (III) Fascicular pattern formed by sheets of spindle cells (H and E x400); (IV) Immunoreactivity for HMB45 noted within the neoplastic cells (immunoperoxidase x100)

All patients had normal blood urea and serum creatinine. All had a palpable, non-tender mass in the renal fossa, which crossed the midline in one case each of MLCN, CMN, and AML. [Table 1; S.No. 5, 9, 11]. Three (25%) patients gave a history of hematuria: MLCN (S.No. 1), and both the children with AML (S.No. 11, 12). In children with CMN, the tumor was antenatally detected in one case (25%). There was premature birth in 2 other cases (50%), with the youngest a 31-week pretermer who got operated 3 weeks after birth [Table 1; S.N. 6–9].

Two cases of MLCN, (S.No. 2 and 3) were referred to us as cystic WT based on imaging. FNAC showed benign columnar cells. There was herniation into the pelvis of the kidney in 2 of the 5 patients with MLCN [Table 1 (S.No. 1 and 5) and Figure 1a, b, k, l and m], one of whom presented with an episode of hematuria. Two other patients (S.No. 8, 9) who underwent FNAC to rule out WT were correctly interpreted as CMN.

In case no. 10, FNAC was reported as malignant small round blue cell tumor, consistent with WT. CECT abdomen impression was cystic fat-containing WT or cystic teratoma in a horseshoe kidney. Serum alpha-fetoprotein was 1.8 ng/ml. The CECT chest showed two small (<3 mm) subpleural nodules in the left lower lobe lung and on review by radiologist were considered too small to be considered metastases. He received four cycles of vincristine and actinomycin-D based on FNAC before surgery with no reduction in the size of swelling on USG. He underwent right nephroureterectomy with right Hemi isthmusectomy. No plane of differentiation was noted with the upper pole of the kidney or pelvicalyceal system [Figure 3d].

Figure 3

Images of Mature teratoma patient: Computed tomography scans (a and b), intra-operative photographs (c and d), specimen (e), Histopathology (f). (I) Elements from 3 germ layers (H and E, x100); (II) Irregularly shaped glands lined by goblet cells in loose mesenchyme (H and E, x100); (III) Glands lined by goblet cells (H and E, x200); (IV) Interface of tumor with kidney

Case 11 (AML) had clinical features suggestive of tuberous sclerosis complex (TSC) like mental retardation, generalized hypopigmented spots and adenoma sebaceum [Figure 4a and d]. Magnetic resonance imaging brain [Figure 4c] had shown tubers. Referral CECT scan and FNAC were reported as WT. FNAC repeated at our center because of the rapidly enlarging abdominal mass was reported as clusters of malignant cells with moderate pleomorphism and interpreted as renal cell carcinoma. He underwent an uneventful nephroureterectomy of a large renal mass occupying nearly the entire abdomen. Nephroureterectomy with Gerota's fascia was possible in all cases without tumor rupture/spillage or injury to adjacent structures. There was no hemodynamic instability in any of the cases during surgery.

In 2 cases of CMN (S.No. 7, 8) focal capsular breach with extension into perinephric fat was noted on HPE. Lymph node sampling done at the time of nephroureterectomy in S.No. 3 and 8–11 were found to be reactive with no tumor infiltration.

S.No. 11 presented 1 month after nephroureterectomy with adhesive intestinal obstruction, which was managed conservatively. Multiple small AMLs were noted in his right kidney at 3-year follow-up, but renal function tests were normal. Both the children with AML have been handed over to adult urology and nephrology services for long-term followup. All other patients had no complaints in the immediate or long term follow-up of 1.5–12 years (median 3 years) with no evidence of recurrence at the local or distant site, including patients with teratoma and cellular CMN.

DISCUSSION

WT is the most common renal tumor in the age group of 6–119 months (median 36 months). Other renal tumors, both benign and malignant, are rare. In centers following SIOP protocol with initial chemotherapy followed by nephrectomy, a child with a benign tumor may unnecessarily receive chemotherapy unless they are <6 months age. Occasionally, a benign tumor may require only partial nephrectomy. Therefore, it is imperative to know the diagnostic features of benign renal tumors of childhood.

CMN is the most common renal neoplasm diagnosed in the neonatal age with a high prevalence before 2 months of age. Nearly 75% manifest by 6 months age.[3456] Diagnostic confusion with WT and CCSK is likely when they present after 2 months of age.[3] In our study, 3 of the 4 cases presented by 2 months of age with only one case being operated at 5 months age, all of whom presented with a palpable flank mass.[4] We observed that the imaging, external appearance and cut section of the tumor was different in the child who presented at 5 months age compared to all the others who were operated by 2 months age. [Figure 2] In this child, the tumor had a mutilobulated appearance, covered by a thin transparent capsule and crossed the midline. The delay in seeking surgical treatment may have led to progressive increase in size and necrosis within the tumor. On gross appearance, CMN and CCSK may look similar. However, CCSK has a similar age distribution as WT. In a 2.5-months-old male baby, who underwent nephroureterectomy, the solid, homogenous tumor with the whorled appearance and firm consistency on cut section and the age of the child prompted a diagnosis of CMN. The HPE however showed typical features of CCSK showing monotonous array of oval to spindle cells with vacuolated cytoplasm and indistinct borders set against a variably myxomatous stroma and the baby was excluded from the study. The histopathologic classification of CMN includes three subtypes: classic (24%), cellular (66%), and mixed (10%).[45] Barrantes et al reported a M:F ratio of 5:4 in conventional CMN and 2:1 in the atypical cellular CMN.[6] In our study also, the M:F ratio in cellular CMN was 2:1. An overview of 306 published cases showed that CMN has an extremely good prognosis. It has a relapse rate of 4%, mostly seen in cellular CMN.[4] Howell et al. in 1982 reported relapse in one of 51 cases, 6 months after surgery, which was associated with intraoperative rupture.[7] After surgical excision and chemotherapy, their patient was free of the disease at 18-month follow-up. In our study, 3 of the 4 cases (75%) had a cellular subtype on HPE with one (S.No. 6) showing local adherence and a highly vascular capsule. Significantly enlarged draining vessels were noted in 2 cases of cellular CMN (S.No. 6, 9). Focal capsular breach with the involvement of perinephric fat was seen in both cellular (S.No. 7) and classic subtype (S.No. 8) on HPE. In Furtwaengler et al.'s study, patients with cellular CMN were significantly older with a median age of 112 days compared to classic CMN with a median age of 6 days.[8] However, in our series, both ends of the age spectrum had cellular CMN. Babies >3 months of age with intra-operative tumor rupture and extensive extrarenal infiltration, incomplete resection, prior open biopsy, positive lymph node, i.e., stage III disease, cellular subtypes or aneuploidy may have to be cautiously considered for additional chemotherapy.[4567] We were able to perform radical nephrectomy in all our cases with no intraoperative spill or capsular tear which is the only line of management required for the majority of patients.[5] CMN is known to have a short risk period for relapse. Our patients were closely followed up with clinical examination and ultrasound in the first 1 year after surgery with no evidence of recurrence during this period and late follow-up.[45678]

Figure 2

Images of Congenital Mesoblastic nephroma patients: Computed tomography scans (a, b, d, g, j; white arrow in a, d, g shows typical hypodense crescent shape in periphery), intra-operative photographs (e and k), specimen/cut sections (c, f, i and l), Histopathology (m). (I) Low magnification depicting fascicles and whorls of bland spindled myofibroblasts and thin collagen fibers entrapping the normal tubules (H and E, x200); (II) Fascicles composed of plump, atypical spindle cells with abundant cytoplasm and vesicular nuclei (H and E, x200); (III) Cellular mesoblastic nephroma depicting areas with brisk mitotic activity (arrow, H and E, x400); (IV) MT stain reveals fine collagen within the stroma (MT x400). MT: Masson's trichrome

MLCN is a benign mixed mesenchymal and epithelial neoplasm of the kidney, which lacks solid areas.[910] The present study had five cases of MLCN, all males, aged 11–16 months at the time of surgery. In a systematic literature review, Granja et al. noted a median age of 18 months and a male predominance of 60.8% in those aged <10 years.[11] In our study, the weight was below normal for age in 3 children, probably due to the pressure effect of the swelling on the gastrointestinal tract. There was a complaint of hematuria in one case (20%) and abdominal pain (20%) in another where the tumor had involved the renal pelvis. [Figure 1a, b, k, l and m]. In a review of 155 cases, including all age groups, patients presented with abdominal mass in 54 (35.2%), abdominal pain in 29 (18.7%), and hematuria in 11 (7.1%).[11] In our series, the tumor was located in the upper and midpole in 3 cases and the lower and mid pole in 1 case. Almost the entire kidney was involved in only one case (S.No. 5), who was symptomatic for 11 months with the mass crossing the midline. His initial USG at a peripheral center had suggested multicystic dysplastic kidney (MCDK) with no function on diuretic renography. He presented to us with failure to thrive, gross abdominal distension, and abdominal pain. The progressive increase in size in MLCN differentiates it from MCDK, where the swelling should reduce with time. Complete nephroureterectomy was performed in all our cases, as mid pole involvement was universal. Both SIOP and NWTS protocols give similar advice with no other treatment required.[10]

The Bosniak classification system of radiology based on morphological changes in renal cysts, presence of calcification, content, and contrast enhancement may help in evaluating complex cystic renal masses.[12] However, it is difficult to differentiate MLCN from malignant cystic partially differentiated nephroblastoma (CPDN), cystic Wilms and a subset of cystic renal cell carcinoma.[101314] The presence of some solid component on imaging indicates WT.[14] Histopathology of excised nephrectomy specimen is the final answer. In CPDN, features are intermediate between that of the benign MLCN and the malignant cystic WT. The inability to take a core biopsy in cystic masses adds to the therapeutic dilemma. In MLCN, the cysts contain clear fluid with chemical composition similar to serum and have normal cytology. In three cases where FNAC was performed at our center, the benign nature of the disease was confirmed.

Renal AMLs are uncommon. Rapid growth of the mass in childhood and adolescence is noted in TSC.[1516] Mesenchymal cells are thought to be the precursor cell for all the components of AML.[15] Development of tortuous vessels and aneurysms which are prone to rupture can lead to hematuria, retroperitoneal hemorrhage, and encroachment into normal renal parenchyma, leading to chronic renal disease. Warncke et al. analyzed 145 patients of TSC and noted an AML incidence of 50.3%.[17] Annual renal USG screening is recommended after 11 years of age for prophylactic treatment and avoiding presentation with hemorrhage or shock.[16] In our series, S.No. 11 with TSC presented at 13-years age with pain abdomen, an episode of hematuria and a large renal swelling crossing the midline. The child had been referred with a preoperative CECT and FNAC reported as WT. The CECT scans had shown no areas of fat attenuation. A repeat FNAC at our center suggested renal cell carcinoma, and he underwent total nephrectomy on the left side.

Partial instead of total nephrectomy is preferred in AML, especially in those with TSC. The criteria for intervention in AML are symptomatic lesions, size >4 cm, associated aneurysm >5 mm and suspicion of malignancy.[16] Selective arterial embolization using different agents have been described in acute hemorrhage, refractory hemodynamic instability as well as prophylactically to shrink the tumor, but have a recurrence rate of 11–40%.[1819] Both the patients in this study underwent total nephrectomy in view of large tumor size, symptoms, location of tumor, and in one case, a pre-operative suspicion of malignancy.

Intrarenal teratoma of the kidney is exceedingly rare with only around 30 cases reported in the literature, with the majority being benign.[20] Idrissi-Serhrouchini et al. reported a 6-month-old girl with immature teratoma in a pelvic kidney.[21] They also reviewed 15 other cases of renal teratoma, 9 of them in the pediatric age group. Mochizuki et al. reported the first case of an immature teratoma arising in the right lower pole and isthmus of a horseshoe kidney.[22] This was similar in tumor location to our patient (S.No. 10), who appears to be only the second case of intrarenal teratoma reported in a horseshoe kidney in the pediatric age group. Apart from horseshoe kidney, association with double ureter, prune belly syndrome, and renal dysplasia have been described.[21] For pure immature teratomas, complete excision of the tumor mass alone is sufficient with 3-year event-free survival rate of >85%.[22] Mature teratomas though benign have a propensity for malignant transformation, thus making long-term follow-up paramount. Our patient is doing well at a follow-up period of 18 months.

Biopsy in many centers is recommended for renal tumors in children >10 years age and where there is clinical and radiological suspicion of non-WT. Due to the presence of a dedicated well-established department of cytopathology and the use of SIOP protocol in our center, FNAC is routinely performed for all cases of WT and others where pre-operative tissue diagnosis is required.[23] Although the accuracy may not be equivalent to core needle biopsy, the advantages are that it is an easy and quick procedure not requiring anesthesia in a small child. To reach more representative areas, image-guided biopsy is preferred. To overcome the handicap of fragmented material, it is centrifuged, thus increasing the cellular yield and processed to form a paraffin cell block. This and the addition of immunocytochemistry improves diagnostic accuracy. Where there is a doubt, core needle biopsy is performed. In this series, while FNAC accurately diagnosed CMN and MLCN, it was not so with teratoma and one case of AML. Renal cell carcinoma is known to occur in TSC patients but with an incidence of <2%.[15] Studies have shown similarity on hematoxylin-eosin staining between epithelioid variant of AML and renal cell carcinoma.[15] WT has heterologous components of blastemal, stromal and epithelial origin, similar to renal teratoma due to a common origin from mesodermal metanephrogenic blastema.[24] WT is also known to be more common in horseshoe kidneys.[22]

In CMN, a hypodense crescent-shaped width was typically found to surround the lesion in 3 of our 4 cases, all of whom had presented in <2 months age [Figure 2a, d and g]. This is not often reported in the literature. Chen et al. have highlighted this typical double-layer sign and attribute it to slow blood flow and delay in filling of the contrast in the peripheral blood sinuses.[25] We also observed that unlike CMN, which tends to grow centrifugally and involve the entire kidney, MLCN tends to involve one or other pole of the kidney compressing the normal kidney in a cranial or caudal direction. Progressive increase in the size of the swelling leading to tumor crossing the midline can occur in benign tumors also which may be due to internal bleeding (S.No. 11) or delay in treatment (S.No. 5, 9). Dilated pelvicalyceal system in the remaining kidney may occur due to the local pressure effect (S.No. 10) or the mass herniating into the renal pelvis (S.No. 5). Small subpleural or pulmonary nodules <5–6 mm in size may be due to previous respiratory tract infections, and a careful history should be elicited to avoid mistaking them for metastases.

The SIOP protocol recommends MLCN and CPDN be treated primarily by surgery, and cystic WT by a combination of neoadjuvant chemotherapy and surgery. However, some authors feel that surgery should be the first line of treatment even when the initial diagnosis is cystic WT due to pre-operative radiological fallacies.[14] We agree with this approach as we had similar issues while dealing with teratoma with a predominant cystic component. Rarely, if the lesion is <4 cm in size and confined to one pole, partial nephrectomy or tumorectomy may be considered as in some cases of metanephric adenoma or inflammatory pseudotumor.

There should be no misconception that benign renal tumors are small. All the tumors seen in this series and most seen in the literature are large and palpable at presentation.[262728293031] An overview of these tumors with typical characteristics are summarized in Table 2. The excellent long-term outcome can be expected in nearly all benign renal tumors provided complete excision is safely achieved.

Table 2

Summary of benign renal tumors in children

Benign renal tumor [41115-17202125-31]	Incidence	Gender	Age range (peak)	Clinical features	USG	CT scan	Histopathology
Congenital mesoblastic nephroma	3%–6.5%	Male > female ratio 1.5:1	Neonate- 1 year (neonate – 2 months)Premature birth common	Palpable mass (76%), hypertension (19%), hypercalcemia (4%), polyuria, haematuria (11%), hyper-reninemia (1%). Congestive heart failure	Solid Hypoechoic areas Occur due to necrosisConcentric hyperechoic and hypoechoic “vascular” ring surrounds tumor on Prenatal USG, 70% have polyhydramnios	Large, heterogenous, solid intra renal mass, with smooth margins. Post contrast enhancement present but less than adjacent renal parenchymaMultiple necrotic areas±hypodense crescent-shaped width surrounding the lesion	Interlacing fascicles of spindle shaped cells with plump nuclei and rounded borders. Frequently entraps normal glomeruli and tubules. Desmin positive (Figure 2m)
Ossifying renal tumor of infancy	<1% very rare	Male > female	Neonate - to 1.5 years (1–3 months)	Intermittent painless hematuria	Heterogeneously echogenic intrarenal mass with posterior acoustic shadowing due to the calcified components of the tumor. Vascularity present	2–3 cm diameter low-attenuation intra-renal mass surrounding a calcified area attached to the papillary region of the renal pyramids, extending in a polypoid fashion into the collecting system. Calcification may resemble Staghorn calculus causing obstructive hydronephrosis (hypointense on T2-weighted MRI)	Spindle cells and osteoblastic cells in a calcified osteoid matrix
Benign lymphatic malformation	Very rare	Female=male	Neonate-79 years (> 20 years)	Incidental diagnosis, palpable mass, obstructive uropathy, flank pain, hematuria, chyluria, hypertension	Well-defined cysts with thin smooth wall which may be irregular. Debris may be due to hemorrhage or infection	Internal septations show contrast enhancement. Density of fluid may be that of water or higher due to mucous, hemorrhage, calcium	Multiple noncommunicating cysts with internal septa lined by endothelium. Factor VIII positive
Teratoma	Very rare	Female > male 3:2	Neonate-adulthood (3 years)	Abdominal mass, pain, anorexia, vomiting, hematuria.Other congenital abnormalities (25%): prune belly, oligodactyly-like syndrome, hypospadias, antenatal diagnosis	Space occupying heteroechoic solid mass with posterior acoustic enhancement, anechoic cystic component with nodular protrusion of solid component into it, no significant vascularity on Doppler	Well defined, large, heterogeneous, encapsulated mass with multiple hypodense and solid areas, thinned out renal parenchyma, fatty tissue with low attenuation values, cyst formation, coarse calcification, clusters of calcific foci	Ectodermal, endodermal and mesodermal elements with heterotopic organogenesis. Mature / immature (Figure 3f)
Multilocular cystic nephroma	2%–3%	Male > female	3 months to 4 years (18 months)	Unilateral flank mass (35.2%)Abdominal pain (18.7%)Hematuria (7.1%)	Well-defined multi cystic lesion with no solid areas. Variable cyst diameter of few mm - cm, septae of variable thickness, no vascularity on Doppler	Well-defined, nonenhancing, encapsulated, multiloculated cystic mass, no solid/soft-tissue mass/calcification. Fluid attenuation values + and a rim of normal parenchyma. Thin, multiple contrast enhancing septa, nonenhanced fluid, no communication with collecting system but portion of the mass may herniate into pelvis (MRI: low T1, high T2 signal intensity)	Septations are composed entirely of differentiated tissue without blastemal or other embryonal elements (Figure 1n)
Metanephric adenoma/nephrogenic adenofibroma/embryonal adenoma	Very rare	Female > male 2:1	15 months - 83 years (fifth to sixth decade)	Asymptomatic or pain, hypertension, hematoma, flank mass, hypercalcemia, polycythemia	Well-defined, solid mass with a central focus of echogenicity Doppler US scan shows hypovascularity	Hyperattenuating mass. Mild homogeneous enhancement within the mass similar to Wilms’ tumor but with a persistent central low-attenuation focus. Calcification seen in 20% cases	Proliferatiing spindle-shaped mesenchymal cells encasing nodules of embryonal epithelium, presence of psammoma bodies, nuclei are homo-geneous and bland without mitotic activity
Metanephric stromal tumor	Very rare	Male=female	First decade (2 years)	Abdominal massHematuriaRecurrent UTIUrinary incontinence	Hypoechoic mass, usually centered in medulla	Nonenhancing, well defined, unilateral, with large central cystic component, and heterologous elements like osseous tissue, cartilage etc.	Alternating cellularity giving nodular appearance, Spindle cells in an Onion skin ring formation around entrapped tubules, (CD34+) diffuse infiltrates perirenal fat
Angio-myolipoma	0.2%–0.6% prevalence, 3% of solid renal masses	TSC, PLLM (20%): Female=maleIn TSC, 80% have AMLSporadic (80%): female > male	TSC: 2–26 years (11 years)Sporadic > fifth to seventh decade	Incidental diagnosis (80%)Palpable flank mass, pain, hematuria, hypertensionTSC features	Hyperechoic lesion (> renal sinus) with posterior acoustic shadowing (only in fat rich lesion)	Low (fat) attenuation (<10 HU) well marginated lesion without true capsule (but maybe fat poor/fat invisible) interposed with solid components. Similar lesion may be present in ipsilateral or contralateral kidney and other organs in TSC. Intermediate density fluid seen with hemorrhage including typical renal notch with vessel entering tumor	Triphasic: adipose tissue, smooth muscle cell, abnormal thick walled blood vessels (Figure 4h)
Leiomyoma	1.5% of benign tumors0.3% primary renal neoplasms5.2% autopsy specimens	Female > male 2:1	6–82 years (47 years)	Incidental diagnosis when small. Mass effect → Pain. Palpable massHematuria Size: 0.5 – 57.5 cm	Well defined, no invasion, hypoechoic irregular central fluid collection, loss of echotexture, hypovascular on DopplerTypes: Sub-capsular, capsular, sub-pelvic	Well circumscribed, peripheral location, exophytic, hyperdense (=muscle) mass, 75% in lower pole, less enhanced compared to renal cortex in corticomedullary phase with progressive homogeneous enhancement. Large tumors have heterogeneous areas due to hemorrhage, degeneration (low SI on T1- and T2-weighted MRI images)	Spindle cells arranged in intersecting fascicles with no mitotic figures, pleomorphism, invasion. Large lesions have cystic degeneration. Actin+, vimentin+Melanoma markers + in capsular variety
Inflammatory pseudotumor	Extremely rare	Male=female	8–76 years (51 years)	Incidental (36%)Lumbar pain (38%), hematuria (28%) constitutional symptoms (23%)History of trauma, surgery, infection, autoimmune process, Epstein–Barr virus infection	Hypo or heterogeneous echoic mass. On Doppler - well defined hypoechoic mass with intra tumoral vascularityMay be bilateral	Low attenuation hypovascular mass (T2 hyperintense enhancing soft tissue mass)	Spindle cell in myxoid background with lymphoid aggregates with patternless pattern. IHC: myofibroblastic nature, vimentin+ smooth muscle actin +, CD34+
Juxtaglomerular cell tumor or reninoma	Extremely rare	Female > male 2:1	Second to third decade	Hypertension, hypokalemia, hyperaldosteronism, high plasma renin activity	Well defined cortical tumor <3 cm size	Isodense or hypodense compared to renal medulla, hypovascular well-defined mass with delayed enhancement	Polygonal tumor cells within vascular stroma and thick walled vessels. CD34+ CD117-

AML: Angio-myolipoma; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; PLLM: pulmonary lymphangioleiomyomatosis; TSC: Tuberous sclerosis complex: USG: Ultrasonography; UTI: Urinary tract infection

CONCLUSIONS

There is a lot of similarity in the presentation of benign renal tumors and WT with incidental diagnosis or presentation with a progressively increasing large, flank mass being common. Occasionally weight loss, hematuria, and pain may be present. The general condition is usually well preserved unless there is delay in presentation. Tumors presenting outside the age spectrum of WT may be easier to diagnose, whereas those presenting around the same time as a WT create confusion. The treating surgeon should be aware of the clinical features and the unique identifying features on CECT. These tumors tend to be well defined, mobile, single, unilateral, mass lesions with no features of invasion, lymphadenopathy, renal vein or inferior vena cava thrombus and metastases. There is invariably some normal ipsilateral renal parenchyma. In doubtful cases, needle biopsy in expert hands is useful to reach a correct preoperative diagnosis.

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Conflicts of interest

There are no conflicts of interest.