INTRODUCTION
Pediatric cystic nephroma is a rare benign renal tumor that usually presents unilaterally. The male:female incidence ratio is approximately 3:1, and pediatric cystic nephromas account for 2% to 3% of primary renal tumors.[1] Few studies have carefully studied pediatric cystic nephromas, and existing reports are ambiguous. During the period from 2006 through 2019, only one case was diagnosed in our hospital. The symptoms of pediatric cystic nephroma are not obvious, and the tumor is rarely fortuitously detected during physical examination. As compared with other childhood renal cystic diseases, diagnosis and differential diagnosis of pediatric cystic nephroma is a considerable challenge. Here we discuss diagnosis of large multicystic nephroma in children and describe two types of renal multicystic lesions in the differential diagnosis of pediatric cystic nephroma.
CASE HISTORY
A 16-month-old boy was admitted to hospital for evaluation of an abdominal bulge observed during bathing. The findings of blood and urine examinations were unremarkable, and no other clinical symptoms were observed. CT showed a mass measuring 15 cm × 12 cm × 11 cm in the left kidney [Figure 1a]. Multiple cystic cavities, with lobular contours and multiple thin divisions, were present in the kidney. Because of the near absence of renal parenchyma [Figure 1b], the patient underwent radical left nephrectomy.
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Figure 1: (a) CT showed that the volume of the left kidney enlarged and the left abdomen bulged. (b) Multiple cystic cavities, with lobular contours and multiple thin divisions, were present in the kidney. No significant renal parenchyma had been found
Postoperative pathological examination of the tumor showed a capsule with clear boundaries, and cystic cavities and intervals of various sizes. The cystic cavities differed; no solid tissue was present, and the capsule contained serous fluid [Figure 2a]. Histopathological examination revealed a cyst wall lined with a single layer of flat, cubic epithelium and some cyst walls lined with nail-like epithelial cells. A substantial number of inflammatory cells and hemorrhage were seen under the local epithelium. The cytoplasm was weakly eosinophilic or transparent, and the cells showed no sign of atypia. Clustered mature renal tubules were present in the local septum, and no immature tissue was found [Figure 2b]. The results of immunohistochemical staining were AE/AE3(+) [Figure 2c] and EMA(+), with no expression of CD10, ER, PR, α-inhibin, or CR. Masson staining showed that collagen fibers were the main tissue component of the cystic wall [Figure 2d]. These findings were consistent with a diagnosis of pediatric multilocular cystic nephroma. After the radical nephrectomy, no recurrence or cystic lesions (in the lung and liver, for example) have been observed during 11 years of follow-up.
Figure 2: (a) The tumor section was composed of cysts and septum of different sizes, each cystic cavity was different, and there was no solid region. Cysts contained serous fluid. (b) The cyst wall was lined with a single layer of flat and cubic epithelium, and some cyst walls were lined with nail-like epithelial cells, with local inflammatory cells, Clustered mature renal tubules were found in the local septum, and no immature tissues were found (H and E; ×100). (c) AE1/AE3 positive (IHC; × 100). (d) Masson staining showed that collagen fibers were the main tissue component of the cystic wall (blue) (Special staining; × 40)
DISCUSSION
Cystic nephroma (CN), also known as multilocular cystic nephroma (MCN), comprises adult and pediatric cystic nephroma. Pediatric cystic nephroma was not considered a unique entity in the WHO classification of renal tumors in 2004 but was instead regarded as cystic partially differentiated nephroblastoma and cystic Wilms' tumor.[2] In the 2016 WHO classification of renal tumors, adult and pediatric cystic nephroma were distinguished on the basis of age, gender, histological morphology, and immunohistochemical characteristics.[3] Adult cystic nephroma is included in the mixed epithelial stromal tumor (MEST) family,[4] while pediatric cystic nephroma is now considered a unique entity possibly related to mutation of the DICER1 gene.[5]
Onset of CN is slow in children, and the disease process is not obvious. Most cases are detected by imaging findings obtained during physical examination, although a few patients present with clinical symptoms. The most common finding in children is an asymptomatic abdominal mass, and some patients have hypertension. Although imaging technologies continue to improve, pediatric renal cystic lesions are complex, which makes it difficult to definitively diagnosis CN before surgery. Diagnosis still largely depends on pathological examination.
Histologically, CN usually appears as a single round tumor with clear boundaries. Resected specimens are multilocular and cystic, and the number and size of cystic cavities vary. The cystic cavities do not communicate with each other. Cystic walls are smooth, and cysts usually contain pale, yellow, thin or bloody liquid. On microscopy, the cystic wall tissue is lined with a single layer of flat, cubic, or nail-like epithelial cells, and the cytoplasm is mostly eosinophilic. The interstitium is fibrous tissue-like and fibroblast-like, and clusters of mature renal tubules may be present in the septum.
Immunohistochemistry reveals expression of AE/AE3 and EMA but no CD10, ER, PR, α-inhibin or CR expression. Studies have reported that pediatric cystic nephroma is related to mutation of the DICER1 gene, and detection of this mutation could help in diagnosing pediatric CN. Currently, the five major pathological diagnostic criteria for CN, as proposed by Boggs, are:
- Multilocular cystic lesions are present;
- Most areas of the cystic cavity are covered with epithelium;
- The cyst and abdominal cavity are not connected;
- Residual renal tissue is outside the tumor capsule and basically normal in structure;
- Immature renal tissue in the cyst septum is not differentiated.[6]
Our diagnosis required us to distinguish between MCDK and CPDN, because these two multicystic renal changes are very similar to CN with respect to imaging findings, gross tumor manifestations, and pathological morphology.
MCDK is the most common cystic kidney disease in children; the incidence of unilateral MCDK is 1:4300 to 1:1000.[7] MCDK is a form of nonhereditary renal dysplasia, usually discovered fortuitously,[8] and is diagnosed by prenatal ultrasound. Typical findings include presence of several noncommunicating cysts of varying size, with thin cyst walls and no identifiable normal renal parenchyma. Microscopically, the cyst wall is lined with a single layer of flat, cubic epithelium. The gross manifestations and pathological morphology of the tumor are similar to those of CN. The most important difference from CN is that early ducts, cysts, and nonrenal tissues—such as cartilage, fat, and hematopoietic tissues—are present in MCDK.
CPDN is a rare nephrogenic tumor and a rare type of Wilms' tumor. Brown first proposed and used the term CPDN, in 1975, and speculated that CPDN originates from meta-nephroblastoma and may be homologous to nephroblastoma. CPDN may have fibrous pseudocapsules, and tumors are composed of multiple noncommunicating cysts. There is no swelling of solid nodules in the septum, and the cyst is lined with flat, cubic, and nail-like epithelial cells. The presence of primitive or immature germ tissue, mesenchymal tissue, or epithelial tissue in the interstitium of the cyst wall is essential to distinguishing CPDN from CN. Therefore, during pathological sampling, more material should be taken from solid or thicker tissue, to prevent misdiagnosis due to omission of nephroblastoma components.
Because pediatric renal cystic lesions are complicated and often yield similar imaging and tumor findings, diagnosis requires careful pathological examination. If children with cystic nephroma have no symptoms or low-volume cysts, follow-up observation is warranted. Surgical treatment is primarily intended to preserve renal function and remove lesions. Surgical treatment (e.g., simple cyst resection, partial nephrectomy, or nephrectomy) is decided on the basis of the size, site, and renal function of the tumor. The prognosis for cystic nephroma is favorable: cystic nephroma seldom recurs and malignant transformation is uncommon.[9,10] Surgical resection remains the treatment of choice for recurrence.
Differentiating pediatric cystic nephroma from other cystic nephromas requires comprehensive examination for cystic lesions in the lungs and liver and identification of any family history of cystic nephroma. Because pediatric cystic nephroma might be linked to mutation of the DICER1 gene, detection of this mutation could help in diagnosing pediatric cystic nephroma. When tumor volume is small, pediatric cystic nephroma is easily misdiagnosed as MCDK or other renal cystic diseases. To ensure accurate diagnosis, a large sample should be collected for pathological diagnosis, especially from thick or solid tissue. Careful clinical, histological, immunohistochemical, and molecular analysis is essential for correct diagnosis. Furthermore, nephrons should be preserved to the greatest extent possible. Because of the possibility of local recurrence or metastasis, long-term observation is recommended.
Ethics approval and consent to participate
Ethical approval was obtained from the ethical committee from the Kunming Children's Hospital, Kunming, China.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
The authors would like to thank the patient and his family for their consent to publish this report.
REFERENCES
1. 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
2. Greco F, Faiella E, Santucci D, Lisi D, Vullo GL, Zobel BB, et al Ultrasound imaging of cystic nephroma J Kidney Cancer VHL. 2017;4:1–9
3. de Kock L, Geoffrion D, Rivera B, Wagener R, Sabbaghian N, Bens S, et al Multiple DICER1-related tumors in a child with a large interstitial 14q32 deletion Genes Chromosomes Cancer. 2018;57:223–30
4. Li Y, Pawel BR, Hill DA, Epstein JI, Argani P. Pediatric cystic nephroma is morphologically, immunohistochemically, and genetically distinct from adult cystic nephroma Am J Surg Pathol. 2017;41:472–81
5. Cajaiba MM, Khanna G, Smith EA, Gellert L, Chi YY, Mullen EA, et al Pediatric cystic nephromas: Distinctive features and frequent DICER1 mutations Hum Pathol. 2016;48:81–7
6. Boggs LK, Kimmelstiel P. Benign multilocular cystic nephroma: Report of two cases of so-called multilocular cyst of the kidney J Urol. 1956;76:530–41
7. Cardona-Grau D, Kogan BA. Update on multicystic dysplastic kidney Curr Urol Rep. 2015;16:67
8. Scala C, McDonnell S, Murphy F, Leone Roberti Maggiore U, Khalil A, Bhide A, et al Diagnostic accuracy of midtrimester antenatal ultrasound for multicystic dysplastic kidneys Ultrasound Obstet Gynecol. 2017;50:464–9
9. Masieri L, Sessa F, Cini C, Sessa M, Vanacore D, Tasso G, et al Robot-assisted nephron-sparing surgery for cystic nephroma in a pediatric patient: A case report J Endourol Case Rep. 2019;5:7–9
10. Sun BL, Abern M, Garzon S, Setty S. Cystic nephroma/mixed epithelial stromal tumor: A benign neoplasm with potential for recurrence Int J Surg Pathol. 2015;23:238–42
