Kidney tumor
Childhood tumors
Pediatric cystic nephroma
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PubMed Search: Pediatric [TIAB] cystic nephroma
Table of Contents
Definition / general | Essential features | Epidemiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Molecular / cytogenetics images | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Anderson D, Tretiakova M. Pediatric cystic nephroma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumorpediatric.html. Accessed June 7th, 2023.
Definition / general
- Uncommon, benign, exclusively cystic neoplasm of the kidney; lacks immature nephroblastic elements or solid growth (Hum Pathol 2016;48:81)
Essential features
- Multicystic neoplasm, often found in children under 4 years old, composed of fibrous septa and differentiated tubules
- Correlation to DICER1 mutations
- Excellent prognosis
Epidemiology
- Pediatric cystic nephroma (PCN) occurs most commonly in children younger than 4 years old, most of whom are boys (Am J Surg Pathol 2016;40:1591)
- Familial cases have been linked to DICER1 germline mutations and familial pleuropulmonary blastoma (PPB), whose main phenotypic spectrum includes PPB, PCN, ovarian Sertoli-Leydig tumors and multinodular goiter and less commonly, pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma and medulloepithelioma (Hum Pathol 2016;48:81)
Clinical features
- Palpable abdominal mass may be incidentally found by parents, caretakers or during routine physical examination
- Most often unilateral but familial forms may present bilaterally (J Med Genet 2010;47:863)
Diagnosis
- Imaging modalities (e.g., ultrasound, CT, MRI) show a multilocular cystic encapsulated mass
- Partial or radical nephrectomy will show diagnostic features
Radiology description
- On CT / MRI, appears as a cystic, multilocular mass, often with pseudocapsule defined as a thin rim of tissue demarcating the margin of the lesion from the adjacent renal parenchyma; may abut the renal pelvis or show protrusion / herniation into the renal pelvis (Hum Pathol 2016;48:81, Radiographics 1995;15:653)
- Ultrasonographic findings are multiple anechoic spaces separated by thin septa (Radiographics 1995;15:653)
Radiology images
Images hosted on other servers:
Large mass occupying left side of the abdomen
Multicystic mass
Mass extending into the left renal pelvis (arrows)
Low attenuation mass with multiple separations
Ultrasonography and CT of abdomen
Well circumscribed, huge CN in the right kidney
Prognostic factors
- Prognosis is excellent: overall survival was 100% over a median followup of 2.4 years in one study (J Urol 2007;177:294)
- Presumed transformation to anaplastic sarcoma in rare cases; however, it is unknown whether all anaplastic sarcomas of the kidney arise from pre-existing cystic nephromas
- Anaplastic sarcomas show presence of cysts with solid areas that may be composed of undifferentiated spindle cells with anaplastic changes, benign or malignant chondroid differentiation; less common features include blastemal-like areas, foci of rhabdomyoblastic differentiation and small islands of osteoid
- Co-occurrence of TP53 mutation may be present with DICER1 mutation
- Longitudinal risks for transformation, responsiveness and prognosis are unknown
- References: Mod Pathol 2018;31:169, Mod Pathol 2014;27:1267
Case reports
- 5 month old girl with pleuropulmonary blastoma in association with cystic nephroma and DICER1 syndrome (Radiology 2014;273:622)
- 7 month old girl with histologic features predominately of cystic nephroma but with foci containing atypical mitotic figures and anaplastic nuclei thought to be nascent anaplastic sarcoma (Hum Pathol 2016;53:114)
- 16 month old girl with multilocular cystic renal tumor extending into the renal pelvis and ureter (J Urol Surg 2014;1:39)
- 2 year old girl with pediatric cystic nephroma and pleuropulmonary blastoma with mutation analysis and pedigree (BMC Cancer 2017;17:146)
- 8 year old girl with DICER1 mutation, anaplastic sarcoma and septated renal cysts, thought to be cystic nephroma (Pediatr Blood Cancer 2016;63:1272)
- 9 year old boy with bilateral and recurrent pediatric cystic nephroma (Can Urol Assoc J 2021;15:E290)
Treatment
- Adequately treated by resection with excellent prognosis if completely excised (J Urol 2007;177:294)
Gross description
- Relatively large (9 cm average diameter) cystic lesion, well circumscribed from the surrounding normal kidney
- Multiple smooth variably sized (mm to cm) cysts with clear fluid
- Thin septa with no expansile nodules altering cyst contours (Sebire: Diagnostic Pediatric Surgical Pathology, 1st Edition, 2009)
- Often adjacent, abutting, protruding or in direct contiguity to pelvicaliceal structures (Hum Pathol 2016;48:81)
Gross images
Contributed by Daniel Anderson, M.D., M.B.A.
Bulging mass
Multicystic
Thin septa and fine vasculature
Images hosted on other servers:
Specimen after nephrectomy
Multiple smooth walled cysts separated by septa
Microscopic (histologic) description
- Multicystic architecture with variably sized simple cysts lacking immature nephrogenic elements, solid areas and cytologic atypia
- Cystic septa are usually hypocellular and fibrous with variable amounts of mixed inflammation and rarely differentiated tubules
- Focally increased subepithelial cellularity may be present either due to spindle cells or inflammation
- Wavy / ropy collagen is absent
- Cyst lining epithelium is flattened to cuboidal, with frequent hobnailing
- No epithelial complexity (branching glands, papillary projection, cribriforming)
- Partial or complete fibrous pseudocapsule often containing entrapped tubules and glomeruli; some tumors intermingle with normal parenchyma (Hum Pathol 2016;48:81)
Microscopic (histologic) images
Contributed by Daniel Anderson, M.D., M.B.A.
Cystic nephroma
Adjacent renal parenchyma
Cystic nephroma flat
Cuboidal, hobnail, flat
Cystic nephroma with hobnailing
Positive stains
- ER positive in subepithelial stromal cells; PCN usually shows stronger and more diffuse positivity in contrast to adult cystic nephroma (Am J Surg Pathol 2017;41:472)
Negative stains
Molecular / cytogenetics description
- DICER1 is a multidomain protein with 2 type III endoribonucleases
- Involved in maturation of several classes of small noncoding RNAs such as miRNAs (Nat Rev Cancer 2014;14:662)
- PCNs usually carry DICER1 mutations, which may be somatic or germline
- Majority of mutations are nonsense and frameshift (truncating) substitutions and missense substitutions
- Somatic mutations often involve RNase IIIb and germline mutations may involve multiple DICER1 domains (Nat Rev Cancer 2014;14:662, Hum Pathol 2016;48:81, Mod Pathol 2014;27:1267)
Molecular / cytogenetics images
Images hosted on other servers:
DICER1 protein domains and mutations
Videos
Pediatric renal tumors: molecular diagnostics and COG updates
Sample pathology report
- Left kidney, partial nephrectomy:
- Pediatric cystic nephroma; margins are negative (see comment)
- Comment: Pediatric cystic nephroma is characterized by mutations in the DICER1 gene and may occur as a part of DICER1 syndrome. Clinical correlation and correlation with germline DICER1 mutation analysis is recommended.
Differential diagnosis
- Adult cystic nephroma:
- Separate pathologic entity mainly in women who are > 30 years and lack the DICER1 mutation (Hum Pathol 2016;48:81, Am J Surg Pathol 2016;40:1591)
- Usually have thicker septa composed of more cellular ovarian type stroma and ropy / wavy collagen
- Stromal cells are often inhibin positive at least focally while PCN is inhibin negative
- ER positivity is seen in both but typically more diffuse and intense in PCN (Am J Surg Pathol 2017;41:472)
- Segmental polycystic kidney disease:
- Clinical, radiologic correlation and family history may be helpful
- Lack of well defined fibrous wall
- Extension of cysts into the adjacent renal parenchyma with intermingling of nephrons; in contrast, PCN usually pushes aside native nephrons
- Lack of DICER1 mutation
- Cystic partially differentiated nephroblastomas and cystic Wilms tumor:
- Cystic Wilms tumor has immature nephrogenic elements plus solid nodules distorting the septal contours (Hum Pathol 2016;48:81)
- Both lack DICER1 mutations (Mod Pathol 2014;27:1267)
- Cystic renal dysplasia:
- Usually bilateral and diffuse
- Other cystic lesions of the kidney
Board review style question #1
A 2 year old boy with metastatic pineoblastoma was noted to have a palpable kidney mass. CT imaging showed a low attenuating cystic mass arising from the left kidney. Partial nephrectomy was performed and showed the above morphology on H&E. Given the findings, what syndromic condition needs to be considered?
- Denys-Drash Syndrome
- DICER1 syndrome
- Hereditary retinoblastoma
- Von Hippel-Lindau (VHL) syndrome
Board review style answer #1
B. DICER1 syndrome. The image shows features of pediatric cystic nephroma. DICER1 syndrome is characterized by an increased risk of developing pleuropulmonary blastoma, multinodular goiter, pediatric cystic nephroma, Sertoli-Lydig cell tumors and embryonal rhabdomyosarcoma. Less commonly, DICER1 mutations have been documented in pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma and medulloepithelioma, among others (Acta Neuropathol 2014;128:583, Acta Neuropathol 2014;128:111, Hum Genet 2014;133:1443, Eye (Lond) 2013;27:896).
Hereditary retinoblastoma is associated with pineablastoma and retinoblastoma. VHL is associated with hemangioblastomas, pheochromocytomas, renal cell carcinomas and endolymphatic sac tumors. Denys-Drash syndrome is a WT1 related Wilms tumor syndrome and associated with disorders of sexual development and Wilms tumor.
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Reference: Pediatric cystic nephroma
Hereditary retinoblastoma is associated with pineablastoma and retinoblastoma. VHL is associated with hemangioblastomas, pheochromocytomas, renal cell carcinomas and endolymphatic sac tumors. Denys-Drash syndrome is a WT1 related Wilms tumor syndrome and associated with disorders of sexual development and Wilms tumor.
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Reference: Pediatric cystic nephroma
