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Extrarenal nephroblastomatosis in children: a report of two cases
© Wu et al.; licensee BioMed Central Ltd. 2014
Received: 24 June 2014
Accepted: 29 September 2014
Published: 6 October 2014
Extrarenal nephroblastomatosis is a rare entity which occurs in retroperitoneum and inguinal region predominantly. Here we report two cases of primary extrarenal nephroblastomatosis of Han Chinese in Asian in unusual locations, one is located in testis and paratestis, and the other is paraspinal cord.
Patient 1 was a 19-month-old boy with a hard and nodular mass adherent to the left testis in inguinal region. Patient 2 was a 9-month-old boy with a 1 × 0.7 × 0.4 cm mass in spinal canal at the midline thoracolumbar region. Histological examinations of the two patients after operations revealed extrarenall nephroblastomatosis with multiple nephrogenic foci, composed of immature glomeruli, tubules and blastemal cells.Then the patients were closely monitored without adjuvant chemotherapy, and has been alive and well without any recurrence for >6 months.
Most nephrogenic rests remain subclinical, and thus, complete excision of the lesion with conservative treatment is recommended. Otherwise, nephrogenic rests are close associated with Wilms tumor and regular follow-up is required to ensure early detection of malignant transformation.
Extrarenal nephroblastomatosis, also called ectopic immature renal tissue (EIRT) [1–3], extrarenal nephrogenic rest (ENR) [4, 5], hamartoma with primitive renal tissue  and mesonephric remnant tissue , has been reported only rarely in the world literature. This unusual lesion is often associated with extrarenal Wilms tumor. However, the mechanism underlying the development and persistence of extrarenal nephrogenic rests remains unclear.
We retrospectively reviewed our hospital records of the past 10 years for cases of nephroblastomatosis and nephroblastoma (Wilms tumor), and identified only two cases of extrarenal nephroblastomatosis, one in the inguinal canal and the other in the vertebral canal. Here, we describe the clinical characteristics, diagnosis, treatment and embryological implications in these two cases.
Kidney development, which is also called nephrogenesis, is a complex process involving tissues with two distinct embryological origins: nephrogenic and ductogenic . Nephrogenic tissue develops from the intermediate mesoderm and proceeds through a series of three successive phases: pronephros, mesonephros and metanephros. This process normally ceases after 36 weeks of gestation, at which time, the metanephric blastema in the kidney disappears . Occasionally, the nephrogenic blastema fails to mature into normal renal parenchyma, and the persistent blastemal tissue is then referred to as nephrogenic rests, which may undergo oncogenic mutation to form a malignant embryonal tumor known as nephroblastoma. On histological examination, nephrogenic rests usually appear as aggregates of abnormally persistent embryonal nephroblastic tissue with small clusters of blastemal cells, tubules and occasional glomeruli, with a variable amount of admixed fibrous stroma. Nephrogenic rests can be unifocal, multifocal or diffuse. The term nephroblastomatosis is used to refer to diffuse or multifocal nephrogenic rests or their derivatives . Nephrogenic rests can be subclassified into perilobar nephrogenic rests and intralobar nephrogenic rests, according to their location in relation to the renal lobe on histological examination. Occasionally, nephrogenic rests are found in ectopic sites, such as the inguinal canal , lumbosacral area [3, 9–12], adrenal gland , thorax [14, 15], colon  and heart . There are two possible distinct fates for nephrogenic rests: to be an isolated developmental abnormality, or the early stage of a neoplastic process, with the latter being more clinically significant. Most nephrogenic rests become dormant, mature or spontaneously regress. Some undergo hyperplastic overgrowth, which is hypothesized to be an intermediate, pre-neoplastic stage in the process of tumorigenesis. Only a small number undergo a neoplastic induction to transform into Wilms tumor, which is the most common malignant renal neoplasm in children .
Differential diagnosis between extrarenal nephroblastomatosis and extrarenal nephroblastoma is mandatory when ectopic immature renal tissue is found. Sometimes it is difficult to distinguish ectopic nephrogenic rests from Wilms tumor on histology, and it is especially difficult to distinguish between a proliferative nephrogenic rest and a small Wilms tumor . Generally, nephroblastoma tends to form round nodules enclosed in a fibrous pseudocapsule owing to its rapidly expansile growth. On histological examination, the lesion comprises nephrogenic tissues, such as blastemal, epithelial (tubular and glomeruloid) and mesenchymal elements. The distinguishing characteristic of nephroblastoma is frank atypia including disordered structures, atypical mitoses and marked pleomorphism. Otherwise, approximately 5% of Wilms tumors show anaplastic cells, which is a typical characteristic of malignant, indicating poor prognosis [20, 21]. In contrast, the lesion in nephroblastomatosis usually consists of small multiple microscopic nests and islets. Mitoses are usually sparse, except in proliferative nodules, which exhibit high mitotic rates and moderate pleomorphism, but no obvious atypia. Proliferative nephrogenic rests invariably show striking enlargement, but lack the peritumoral pseudocapsule characteristic of Wilms tumor.
In both our patients, the possible differential diagnoses included teratoma, a neoplasm originating from testicular tissue, metastasis and malignancies other than Wilms tumor. The nephrogenic epithelial elements (glomeruli, tubules) in the two cases had differentiated to a rather advanced degree, and rare mitoses with no atypia were found scattered within the dense fibrous tissue, indicating a benign neoplasm. The diagnosis of teratoma was excluded due to the lack of other teratomatous non-nephrogenic tissues.
The ectopic nephrogenic rests were thought to have originated from mesonephric or metanephric tissue. In the few published studies on this topic, ectopic nephrogenic rests have been reported predominantly in the retroperitoneum and inguinal region . In our first patient, the mass was attached to the testis, which is consistent with an nephrogenic rest arising from mesonephric tissue, because the mesonephros is associated with the developing gonad, embryologically . There have also been several case reports of intraspinal nephrogenic rests located in the lumbosacral area and frequently associated with spinal dysraphism [3, 10]. This peculiar association of spinal abnormalities with nephrogenic rests in the lumbosacral region, where the metanephros comes closest to the spinal cord , supports the hypothesis that neural tube abnormalities interfere with the migration of renal tissue and thereby result in ectopic nephrogenic rests [4, 12]. However, in our second patient, the lesion was located in the lower thoracic region, indicating that nephrogenic remnants may be trapped between the dura and the developing spinal cord early during nephrogenesis.
From the scarce literature available on this subject, we conclude that most nephrogenic rests can be expected to remain subclinical, and thus, complete excision of the lesion with conservative treatment is recommended. However, it is reported that approximately 40% Wilms tumors were associated with nephrogenic rests . Owing to the close association between renal nephrogenic rests and Wilms tumor, regular follow-up is required for such lesions until the period of risk has ended. This ensures the detection of malignant transformation at an early stage [25, 26].
Written informed consent was obtained from the patient’s parents for publication of this case report and any accompanying images. A copy of the written consents is available for review by the Editor of this journal.
The materials and data of the patients have been performed in accordance with the Declaration of Helsink and have been approved by an appropriate ethics committee of Soochow University Affiliated Children’s Hospital.
The authors are grateful to Mrs Ming Zhang and Xiaowei Li for contributing materials essential for the report.
- Goldberg J, Drut R: Ectopic immature renal tissue. Report of two cases. Pathol Res Pract. 1984, 179 (1): 115-123. 10.1016/S0344-0338(84)80074-6.View ArticlePubMedGoogle Scholar
- Ducos R, Warrier RP, MacKenzie F, Evans B: Ectopic immature renal tissue in an infant with undescended testis. Am J Pediatr Hematol Oncol. 1986, 8 (3): 264-266. 10.1097/00043426-198623000-00021.View ArticlePubMedGoogle Scholar
- Alston SR, Fuller GN, Boyko OB, Goscin SA, DiSclafani A: Ectopic immature renal tissue in a lumbosacral lipoma: pathologic and radiologic findings. Pediatr Neurosci. 1989, 15 (2): 100-103. 10.1159/000120451.View ArticlePubMedGoogle Scholar
- Abrahams JM, Pawel BR, Duhaime AC, Sutton LN, Schut L: Extrarenal nephroblastic proliferation in spinal dysraphism. A report of 4 cases. Pediatr Neurosurg. 1999, 31 (1): 40-44. 10.1159/000028829.View ArticlePubMedGoogle Scholar
- Bennett S, Defoor W, Minevich E: Primary extrarenal nephrogenic rest. J Urol. 2002, 168 (4 Pt 1): 1529-View ArticlePubMedGoogle Scholar
- Horster MF, Braun GS, Huber SM: Embryonic renal epithelia: induction, nephrogenesis, and cell differentiation. Physiol Rev. 1999, 79 (4): 1157-1191.PubMedGoogle Scholar
- Charles AK, Brown KW, Berry PJ: Microdissecting the genetic events in nephrogenic rests and Wilms’ tumor development. Am J Pathol. 1998, 153 (3): 991-1000. 10.1016/S0002-9440(10)65641-6.View ArticlePubMedPubMed CentralGoogle Scholar
- Beckwith JB, Kiviat NB, Bonadio JF: Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol. 1990, 10 (1–2): 1-36.View ArticlePubMedGoogle Scholar
- Gaskill SJ, Kagen-Hallett K, Marlin AE: Diastematomyelia associated with ectopic renal tissue. Pediatr Neurosci. 1988, 14 (2): 108-111. 10.1159/000120372.View ArticlePubMedGoogle Scholar
- Ibrahim AE, Myles L, Lang DA, Ellison DW: Case of the month: June 1998–2 year old boy with lumbosacral mass. Brain Pathol. 1998, 8 (4): 817-818.PubMedGoogle Scholar
- Posalaky Z, Drake RM, Mawk JR, Franciosi RA, Spencer BH, Athinarayanan PR, Baker TA, Viring N: Ectopic immature renal tissue over the dorsum of lumbar and sacral area in two infants. Pediatrics. 1982, 69 (3): 336-339.PubMedGoogle Scholar
- Horenstein MG, Manci EA, Walker AB, Dehner LP: Lumbosacral ectopic nephrogenic rest unassociated with spinal dysraphism. Am J Surg Pathol. 2004, 28 (10): 1389-1392. 10.1097/01.pas.0000131557.49774.29.View ArticlePubMedGoogle Scholar
- Milliser RV, Greenberg SR, Neiman BH: Heterotopic renal tissue in the human adrenal gland. J Urol. 1969, 102 (3): 280-284.PubMedGoogle Scholar
- Kayiran PG, Gumus T, Kayiran SM, Bilge I, Gurakan B: Ectopic intrathoracic kidney with right-sided congenital diaphragmatic hernia. J Pediatr. 2013, 163 (4): 1226-1226. 10.1016/j.jpeds.2013.04.016. e1221View ArticlePubMedGoogle Scholar
- Onuk O, Tas T, Senturk AB, Sinanoglu O, Balci MB, Celik O, Nuhoglu B: Right-Sided Bochdalek Hernia with Intrathoracic Ectopic Kidney in an Advanced-Age Adult: A Case Report. Urol Int. 2014, [Epub ahead of print]Google Scholar
- Jain D, Martel M, Reyes-Mugica M, Parkash V: Heterotopic nephrogenic rests in the colon and multiple congenital anomalies: possibly related association. Pediatr Dev Pathol. 2002, 5 (6): 587-591. 10.1007/s10024-002-0055-4.View ArticlePubMedGoogle Scholar
- Milliser RV, Greenberg SR, Neiman BH: Heterotopic renal tissue in the human heart. J Urol. 1972, 108 (1): 21-24.PubMedGoogle Scholar
- Beckwith JB: Precursor lesions of Wilms tumor: clinical and biological implications. Med Pediatr Oncol. 1993, 21 (3): 158-168. 10.1002/mpo.2950210303.View ArticlePubMedGoogle Scholar
- Beckwith JB: Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am J Med Genet. 1998, 79 (4): 268-273. 10.1002/(SICI)1096-8628(19981002)79:4<268::AID-AJMG7>3.0.CO;2-I.View ArticlePubMedGoogle Scholar
- Vujanic GM, Sandstedt B, Harms D, Kelsey A, Leuschner I, de Kraker J: Revised International Society of Paediatric Oncology (SIOP) working classification of renal tumors of childhood. Med Pediatr Oncol. 2002, 38 (2): 79-82. 10.1002/mpo.1276.View ArticlePubMedGoogle Scholar
- Breslow NE, Churchill G, Nesmith B, Thomas PR, Beckwith JB, Othersen HB, D’Angio GJ: Clinicopathologic features and prognosis for Wilms’ tumor patients with metastases at diagnosis. Cancer. 1986, 58 (11): 2501-2511. 10.1002/1097-0142(19861201)58:11<2501::AID-CNCR2820581125>3.0.CO;2-V.View ArticlePubMedGoogle Scholar
- Oottamasathien S, Wills ML, Brock JW, Pope JCT: Primary extrarenal nephroblastomatosis. Urology. 2007, 69 (1): 184-e183-184View ArticlePubMedGoogle Scholar
- Strand WR, Chou P, Pero JE, Kaplan WE: Extrarenal Wilms tumor occurring in the inguinal canal. J Urol. 1990, 143 (4): 783-785.PubMedGoogle Scholar
- Summers BA, de Lahunta A, McEntee M, Kuhajda FP: A novel intradural extramedullary spinal cord tumor in young dogs. Acta Neuropathol. 1988, 75 (4): 402-410. 10.1007/BF00687794.View ArticlePubMedGoogle Scholar
- Caiulo VA, Latini G, Cataldi L, De Felice C: Nephrogenic rests: their frequency and their fate. J Pediatr Hematol Oncol. 2007, 29 (6): 361-363. 10.1097/MPH.0b013e3180601058.View ArticlePubMedGoogle Scholar
- Hennigar RA, O’Shea PA, Grattan-Smith JD: Clinicopathologic features of nephrogenic rests and nephroblastomatosis. Adv Anat Pathol. 2001, 8 (5): 276-289. 10.1097/00125480-200109000-00005.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/255/prepub
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