Uncommon renal tumors in children: A single center experience.

AIMS: Scrutiny over the clinical behaviors, management, and the final outcome of some rare renal neoplasm in order to find out some hidden facts about these tumors which are playing an important role in the disease course and its management.
MATERIALS AND METHODS: Retrospective evaluation of uncommon (non-Wilms') renal neoplasm in the pediatric population in a tertiary care center. Fifteen cases of uncommon renal tumors were treated in our institution over the last 5 years (January 2008 to December 2012). The cases were tabulated in the form of age, sex, mode of presentation, preoperative investigations, intraoperative grading, pathological type, postoperative management and the final outcome. The patients were followed up for 2 years (clinically every 3 months and ultrasonography abdomen in every 6 months for first 2 years) in order to see any evidence of recurrence and complications related to postoperative chemotherapy.
RESULTS: Out of 15 cases, four cases were clear cell sarcoma (CCS) (26.6%), three cases were rhabdoid tumor (20%), three cases were congenital mesoblastic nephroma (20%), two cases were multilocular cystic nephroma (13.3%), two cases were renal teratoma (13.3%), and one case of teratoid Wilms' tumor (6.6%). There were two deaths (one CCS and one rhabdoid tumor) due to chemotherapy-related toxicity but no recurrence. Three patients were lost during postoperative follow-up; ten patients are doing well and getting a regular visit in the follow-up clinic.
CONCLUSION: The clinical presentations of these uncommon renal tumors are similar to that of Wilms' tumor. Thus, preoperative diagnosis is difficult even with modern imaging techniques. Some of these tumors (CCS, rhabdoid tumor) are rapidly progressing and have a poor outcome. Hence, early intervention in the form of complete surgical resection of the tumor (whenever possible) and postoperative chemo/radiotherapy are imperative for fruitful outcome.

INTRODUCTION

Nephroblastoma (Wilms’ tumor) is the most common renal tumor in childhood. It accounts for more than 90% of renal tumor. Some unusual renal tumors like clear cell sarcoma kidney (CCSK), rhabdoid tumor kidney (RTK), congenital mesoblastic nephroma (CMN), multilocular cystic nephroma (MCN), teratoid Wilms’, and renal teratomas are found infrequently. Clinically, they are indistinguishable from Wilms’ tumor. Hence, preoperative diagnosis of non-Wilms’ renal tumor are often difficult. They are usually diagnosed by tissue biopsy in the form of histopathological examination (HPE) and/or immunohistochemistry (IHC). A few case series of uncommon renal tumors are reported in literature till now. We have undertaken a retrospective study of non-Wilms’ renal tumors in our institution. Each tumor has been evaluated individually in terms of its presentation, preoperative investigations, preoperative chemotherapy, intraoperative findings, postoperative recovery, histopathological findings, postoperative chemotherapy, final outcome, and follow-up protocol. The results are tabulated, evaluated, and compared with the other available concerned articles of uncommon renal tumors.

MATERIALS AND METHODS

This is a retrospective analysis of uncommon (non-Wilms’) renal tumors in children. We have intentionally excluded Wilms’ tumor from this study. The study comprised of 15 patients, out of which 11 were male and 4 were female. Age ranged from 1 day to 8 years. All patients were diagnosed clinically as a renal lump. Practically, most of the cases were preoperatively taken as Wilms’ tumor. All the patients were investigated in the form of complete hemogram, urine routine examination, chest X-ray, ultrasonography (USG) whole abdomen, and contrast enhanced computed tomography (CECT). Magnetic resonance imaging, magnetic resonant urogram, and urine for venillylmandelic acid (VMA) were done in selective cases. Neo-adjuvant chemotherapies were given in two cases to make them amenable for complete surgical tumor resection. Radical nephrectomy and surgical staging were done in all cases. Postoperative chemotherapy and radiotherapy were given according to the histopathological reports as we had no facility of IHC in our institution.

The patients were followed up clinically in every 3 months, USG abdomen in every 6 months for first 2 years. Then, every six monthly evaluation (abdominal examination for any lump, blood pressure measurement, and serum urea/creatinine estimation) in the follow-up clinic for another 3 years.

RESULTS

We had three patients of unilateral RTK. All the patients had undergone nephroureterectomy, and they had an uneventful postoperative recovery. Postoperative HPE confirmed RTK [Figure 1]. One of them expired during postoperative chemotherapy probably due to chemotherapy-induced toxicity. One patient did not come to follow-up clinic for postoperative chemotherapy. Another patient had developed skull metastasis in postoperative period, but he did not seek further treatment.

Figure 1

Clinical photograph showing flank abscess with renal mass, radiological picture showing large heterogeneous mass, indistinct margin, and areas of necrosis consistent with rhabdoid tumor of kidney

We had treated four patients of CCSK. Among them, one had presented with an advanced stage of the tumor with metastasis. Moreover, we had to administer four cycles of neo-adjuvant chemotherapy in this case in the form of actinomycin-D, vincristine, and doxorubicin. All four patients had undergone radical nephroureterectomy. Histopathological reports showed the classic type of CCS in all four patients [Figure 2]. Postoperative chemotherapy (DVC and E) was administered in all cases. Local irradiation was needed in one patient who had a large renal tumor and with bone metastasis. Even with all measure, this patient had died after a period of 18 months. One patient was lost to follow-up after completion of chemotherapy. Two patients are doing well.

Figure 2

Histopathological picture and computed tomography scan picture suggestive of clear cell sarcoma of kidney

We had treated two patients of renal teratoma. One of them was a 1-month-old male child who had immature teratoma. The patient had received postoperative chemotherapy in the form of bleomycin, etoposide, and cisplatin (BEP). In 1 year follow-up, there was no recurrence. Another patient was a 3-year-old female child who had mature teratoma. Hence, postoperative chemotherapy was not given in this case. There was no recurrence and patient was doing well in 1½ years follow-up.

In our series, we had found one case of teratoid Wilms’ tumor. A 4 years girl had presented with the right flank mass of 3 months duration with intermittent fever. USG abdomen had shown large, sharply demarcated, hyperechoic mass of 10 cm × 5 cm × 4 cm size located at the renal area. CECT abdomen had suggested the lesion as nephroblastoma. Color Doppler study had excluded the intravascular extension of the tumor. Right nephrectomy was done. Biopsy reports had shown teratoid Wilms’ tumor with favorable histology. We had given postoperative chemotherapy (Actinomycin-D and vincristine). On 2 years follow-up, the patient was doing well.

We had three cases of CMN. One patient was brought to us at the age of 1 day with antenatally detected renal mass. She also had associated with omphalocele. Other two patients (male) had presented at the age of 3 and 8 months, respectively. After preoperative investigations (USG, CECT whole abdomen), we had performed nephrectomy in all three patients. Histopathological reports had shown a classical variant of CMN in two cases [Figure 3] and a cellular variant of CMN in one case. We had given chemotherapy in a cellular variant of CMN in the form of vincristine, cyclophosphamide, and doxorubicin. This patient had developed psoas abscess on opposite side after 9 months which was treated accordingly. All three patients were doing well and there was no evidence of tumor recurrence or metastasis during the follow-up over 1 year.

Figure 3

Clinical photograph showing omphalocele with left renal area fullness, radiological picture showing homogenous renal mass with displaced small kidney, and gross specimen showing large renal mass with areas of necrosis and hemorrhage consistent with congenital mesoblastic nephroma of kidney

Two cases of cystic nephroma were encountered in our series. They had presented with a loin lump and hematuria. USG abdomen had shown cystic lesion with sharp demarcation to that of renal parenchyma. CECT abdomen had suggested multilocular cystic tumor in kidney with sharply demarcated margin without wall thickening or any calcification or contrast enhancement. Nephrectomy was done in these two cases. HPE had suggested cystic nephroma. Postoperative chemotherapy or radiotherapy was not given. Both patients were doing well in 2 year follow-up period.

DISCUSSION

RTK accounts for 2% of all renal tumors. It was described early in 1978 as a rhabdomyosarcomatoid variant of Wilms’ tumor.[1] The term “rhabdoid tumor” was coined by Haas in 1981 because of absence of muscle differentiation. RTK is the most aggressive renal tumor in pediatric age group. Usually, it presents in advanced stage and resistant to chemotherapy.[2] Diffuse hematogeneous and lymphatic spread occur in infancy. Both International Society of Pediatric Oncology (SIOP) and Children's Oncology Group/National Wilms Tumor Study Group (NWTSG) have reported a poor outcome for children with RTK. But, in the absence of central nervous metastasis prognosis is good. Prognosis is also good in older children and lower stage of the disease. Unlike Wilms’ tumor it is often associated with hypercalcemia. Macroscopically, it is solid, nonencapsulated with extensive intratumoral hemorrhage and necrosis. Microscopically, it comprises sheets of cells with prominent nucleoli and nuclear pleomorphism. Important histologic features are open vesicular nuclei and scattered hyaline eosinophilic cytoplasmic inclusions of intermediate filament in a whorled pattern. Another important diagnostic feature is integrase interactor 1 protein negativity found in IHC staining.[3] In our series, we encountered three male patients with RTK. They presented with rapidly progressing renal lump. There was no hematuria and no clinical evidence of distant metastasis. One patient had a history of flank abscess which was treated outside in the form of incision drainage and biopsy. HPE showed RTK. We performed nephroureterectomy in all patients. Postoperative chemo started as soon as we get the histopathological reports. Unfortunately, we have lost all the three patients.

CCSK is also known as “Bone metastasing tumor of childhood.” It comprises of 3% of all primary childhood renal tumor. It is classified separately from Wilms’ tumor due to several distinctive features such as unilateral, unicentric in the medullary region of kidney with foci of necrosis and cyst formation, and presence of intracytoplasmic vesicles. CCSK has propensity to permeate through renal and perirenal vascular system.[4] Bone and brain metastasis is the characteristic features of CCSK. CCSK is rare below 1 year of age, peak incidence 3-5 years and is more common in male (male:female = 2:1). Various patterns of CCSK have been described such as classical, myxoid, sclerosing, cellular, epitheloid, palisading verocay body, spindle cell, storiform, and anaplastic. Most common is classic type (90%) where the tumor cell appears as monomorphic with cords or nests of 10 cells separated by fibrovascular septa. Cells in the core of the tumor may assume a spindle shape. Nuclei are overall uniform with fine dirty chromatin without prominent nucleoli. Empty appearing Orphan Annie Eye nuclei are a frequent occurrence. Cytoplasm is sparse with indistinct borders.[5] CCSK is vimentin and Bcl-2 positive. CCSK is managed by aggressive surgical approach followed by chemotherapy and radiotherapy as per NWTSG protocol. Relapses although late are common even in stage-1 tumor. The overall survival is 69%.[5] In this series, we have encountered four patients with CCSK. All patients were diagnosed clinically as renal lump and investigated in the form of blood hemogram, USG, CECT abdomen, chest X-ray, and urinary VMA. One of them had required neo-adjuvant chemotherapy. All the patients had radical nephrectomy and received postoperative chemotherapy with Doxorubicin, vincristine, Etoposide, and Cyclophosphamide. One patient died due to extensive metastasis. One patient had lost to follow-up and two are doing well for last 2 years.

Teratoma arises from pluripotent cells (Germ cells or embryonic cells). Teratoma from embryonic origin usually congenital and occur at extragonadal sites. Germ cell origin teratomas are not essentially congenital but usually occur at gonads. It is an encapsulated tumor contains tissue or organ components resemble normal derivatives of more than one germ layer. Tissues of teratoma are different from surrounding tissues contains hair, tooth, bone, brain, eyes, torso, hands, feet, limbs, etc. Teratoma belongs to tumor known as nonseminomatous germ cell tumor. Gradation of teratoma was proposed by Gonzalez-Crussi.[6] But, any grade of teratoma has the potential for malignant transformation. Teratoma with malignant transformation may contain of somatic (nongerm cell) malignancy such as leukemia, carcinoma, or sarcoma. Teratoma of mixed germ cell type is normally malignant and contains element like endodermal sinus tumor and choriocarcinoma. Complete excision of tumor is recommended whenever possible. Postoperative chemotherapy (BEP) is needed in selective cases like malignant teratoma. During follow-up period apart from clinical examination and imaging, measurement of serum beta human chorionic gonadotropin and alpha-fetoprotein are utmost important both for diagnosis, monitoring successful treatment, and to detect relapse.

The term teratoid Wilms’ was first used by Variend et al. in 1984.[7] It is a variant of Wilms’ tumor. Wilms’ tumor is classically triphasic tumor. The combination of blastemal, stromal, and epithelial cell types is observed. Other elements such as squamous, mucinous epithelium, smooth muscle, adipose tissue cartilage, osteoid, and neurogenic tissue are occasionally found. Presence of more than 50% heterogeneous component is an essential criterion for diagnosis of teratoid Wilms’ as proposed by Fernandes et al. in 1988.[8] It is a childhood tumor and bilateral involvement is common (38%).[9] It is resistant to both chemotherapy and radiotherapy.[10] In our series, we have treated one case of teratoid Wilms’. The patient had presented with the right-sided renal mass with intermittent fever. We had investigated and performed right nephroureterectomy. The patient is doing well for more than 2 years. Teratoid Wilms’ is an HPE diagnosis.

CMN is the most common renal tumor in newborn and infancy. Bolande et al. were the first to describe the tumor as a separate entity from Wilms’ tumor.[11] Macroscopically, it is a firm tumor. Cut section shows yellowish gray trabeculations like leiomyoma. Three histological subtypes have been described. Classical (24%) looks like infantile myofibromatosis, cellular (66%) looks like infantile fibrosarcoma, and mixed type (10%).[12] Relationship between mixed CMN and two main histologic subtypes is not clear.[13] Classic CMN reflects intrarenal fibromatosis and cellular CMN is intrarenal infantile fibrosarcoma. Most cases of CMN are cured with radical nephrectomy with lymph nodes sampling. Metastasis to lung, liver, brain, and heart have been reported.[1415161718]

Cystic nephroma, also known as MCN, is a rare nongenetic lesion of unknown etiology. According to the “WHO classification of the renal neoplasms,” it is grouped along the mixed epithelial-stromal tumor of the kidney.[19]

Histologic feature include cyst lined by flat, cuboidal, or hobnail epithelium and septa variably lined by fibrous and/or ovarian-like stroma. Clinically, all patients presented to us with renal lump and hematuria. USG and Doppler study of the abdomen revealed no vascularity of the tumor. CECT of whole abdomen showed cystic mass with sharp demarcation with renal parenchyma. No lymphadenopathy or metastasis was found. Radical nephrectomy was done. Cut surface revealed multiple cysts pushing renal pelvis, cysts were filled with serous fluid, and rim of normal renal tissue. Cysts were lined by cuboidal or flattened epithelium. Edmunds reported first case of CN in 1892 as cystic adenoma of the kidney.[20]

CONCLUSION

We had encountered different types of uncommon renal tumors such as CCSK, RTK, CMN, etc., in this study. Among them, RTK had shown a poor prognosis. CCS is an aggressive and rapidly progressive renal tumor, but the final outcome has changed for better with improvised chemo- and radio-therapies. The CMN has very good prognosis as with cystic nephroma and teratoid Wilms’. Another important fact is proper counseling of the parents. It reduces the psychological burden of parents and also ensures to bring the patients at postoperative follow-up clinic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.