cystic nephroma

Digital case

 HPC:367 : cystic nephroma

Images

 https://twitter.com/sarabethrides/status/718953442140667905

Definition: Cystic nephroma (CN) and mixed epithelial and stromal tumor (MEST) are rare benign renal neoplasms that have overlapping clinical and morphologic features, including predominance in middle-aged women, variably cystic architecture, eosinophilic cells, and hobnail cells lining the cysts and ovarian-type stroma.

A cystic nephroma, also known as multilocular cystic nephroma, mixed epithelial stromal tumour (MEST) and renal epithelial stromal tumour (REST), is a type of rare benign kidney tumour.

Cystic nephroma is a rare benign renal neoplasm of uncertain cause. The tumor was originally described by Edmunds in 1892 as a “cyst adenoma”, and since then the spectrum of histologic findings and multiple theories of the pathogenesis of cystic nephroma have given rise to many synonymous terms, including "benign multilocular cystic nephroma" and "ystic nephroblastoma".

The prevalence of this nonfamilial condition is uncertain. Gallo and Penchansky reported cystic nephroma in 2.4% of 165 primary renal neoplasms seen at their institution.

Studies have confirmed a biphasic age and sex distribution:
 Two-thirds of multilocular cystic renal tumors occur in a predominately male pediatric population between 3 months and 2 years old; approximately one-third occur in a mostly female population, with a peak in the 5th and 6th decades of life.
 There is no association with cysts in other organs and only sporadic association with other congenital anomalies.

Symptoms

Cystic nephromas are often asymptomatic. They are typically discovered on medical imaging incidentally (i.e. an incidentaloma).

Presenting symptoms vary with patient age.

Children typically present with a painless, progressively enlarging, palpable abdominal or flank mass that has a variable growth rate and may be discovered incidentally.

Adults can present with a variety of nonspecific signs and symptoms, including abdominal and flank pain, urinary tract infection, and hypertension. Hematuria, either microscopic or gross, can occur in either group.

In a review of 58 patients with multilocular cystic nephroma at the Armed Forces Institute of Pathology, Madewell et al found hematuria to be related to urinary tract infection and, more commonly (as in our patient), to herniation of pedunculated cysts into the renal pelvis.

Variable degrees of obstruction of the renal collecting system can occur due to herniation of the tumor, which can lead to urinary tract infection.

Macroscopy

Cystic nephroma demonstrates gross pathologic features that are indistinguishable from those of CPDN.

A well-circumscribed mass with a thick fibrous capsule contains multiple fluid-filled, noncommunicating cystic spaces separated by connective tissue septa.

Typically, the mass is solitary, unilateral, and arises from the lower pole, although occasionally (as in this case) it may almost completely replace the kidney.

Madewell et al., whose study population consisted of children 4 years old and younger, found that the mass had a mean size of 7.6 × 9.7 cm and the locules ranged from a few millimeters to 2.5 cm.

Calcification is rare. Necrosis and hemorrhage are uncommon but are usually seen in association with herniation of the tumor into the renal pelvis or ureter, which damages the thin layer of transitional epithelium.

Microscopy

At microscopic analysis, the locules are lined by flattened cuboidal or slightly protruding epithelial cells.

The fibrous septa lack the blastemal or other embryonal elements found in CPDN but may contain well-differentiated renal tubules.

Adequate sampling is essential to distinguish between cystic nephroma and CPDN because the blastemal component theoretically portends the risk of Wilms tumor development.

Local recurrence with CPDN was reported in a case of incomplete resection. There have been no reports of cystic nephroma demonstrating local aggressive behavior or of malignant transformation.

Pathologic synopsis

 simple epithelium with hobnail morphology
 ovarian-like stroma
 cysts lined by a simple epithelium with a hobnail morphology
 nuclei of the cyst lining epithelium bulges into the lumen of the cysts,
 Ovarian-like stroma that has a spindle cell morphology, and has a basophilic cytoplasm.

Immunochemistry

Cystic nephromas have an immunostaining pattern like ovarian stroma; they are positive for:
 Estrogen receptor (ER),
 Progesterone receptor (PR) and
 CD10.

Associations

 pleuropulmonary blastoma (pneumoblastoma) (16808637, 10881016)

• association cystic nephroma and pleuropulmonary blastoma (CNPPB syndrome) (16808637, 10881016)

 extralobar pulmonary sequestration (16773421)
  renal angiomyolipoma (10982023)
 juxtaposed cystic nephroma and Wilms tumor (10594137)

Differential diagnosis

 cystic partially differentiated nephroblastoma
 cystic standard nephroblastoma
 cystic mesoblastic nephroma
 other renal cysts

Cystic nephroma is now classified with "cystic partially differentiated nephroblastoma" (CPDN) as a "multilocular cystic renal tumor".

Cystic nephroma and CPDN are histologically distinct but anatomically and radiologically identical. In 1989, Joshi and Beckwith proposed modified terminology and refined diagnostic criteria to help differentiate "cystic nephroma" from "CPDN" and other cystic renal tumors such as "Wilms tumor with cyst formation".

Many diverse disease processes may result in a multiloculated renal mass, including cystic neoplasms, unilateral autosomal dominant polycystic kidney disease, and localized cystic disease of the kidney.

Any solid childhood renal neoplasm may undergo hemorrhage and necrosis and look like a multilocular cystic renal tumor. The presence of solid elements excludes cystic nephroma and implies a more aggressive neoplasm.

Cyst formation occurs in less than 10% of Wilms tumors, and rarely is the growth pattern predominantly cystic.

Cystic nephroma can be differentiated from Wilms tumor by the absence of expansile solid masses of nephroblastomatous tissue.

Cystic nephroma has not been diagnosed antenatally and does not occur in the neonatal period, observations that help distinguish it from clear cell sarcoma and cystic variants of mesoblastic nephroma.

Multicystic dysplastic kidney (MCDK) can be differentiated from cystic nephroma owing to the absence of normally functioning renal parenchyma and to symmetric contrast material excretion at CT by the remaining normally functioning parenchyma in patients in whom a large portion of the kidney has been replaced by cystic nephroma.

In MCDK, it is possible to observe an enhancing central core of solid dysplastic tissue, but this enhancement is different from that of normal renal parenchyma.

Segmental MCDK may occur in the obstructed moiety (typically the upper pole moiety) in patients with complete ureteral duplication. At imaging, it may be possible to distinguish segmental MCDK from cystic nephroma without evidence of complete duplication.

Treatment

Treatment of cystic nephroma consists of surgical excision, which is curative whether nephrectomy or nephron-sparing surgery with tumor-free margins is performed.

Cases

 http://radiographics.rsna.org/content/24/2/589.full

See also

 renal tumors

• renal cystic tumors

 cystic kidneys and renal cysts

Open References

 DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Doros LA, Rossi CT, Yang J, Field A, Williams GM, Messinger Y, Cajaiba MM, Perlman EJ, A Schultz K, Cathro HP, Legallo RD, LaFortune KA, Chikwava KR, Faria P, Geller JI, Dome JS, Mullen EA, Gratias EJ, Dehner LP, Hill DA. Mod Pathol. 2014 Sep;27(9):1267-80. doi : 10.1038/modpathol.2013.242 PMID: 24481001 [Free]

References

 Cystic nephroma/mixed epithelial stromal tumor: a benign neoplasm with potential for recurrence. Sun BL, Abern M, Garzon S, Setty S. Int J Surg Pathol. 2015 May;23(3):238-42. doi : 10.1177/1066896914563391 PMID: 25525149

 Boman F, Hill DA, Williams GM, Chauvenet A, Fournet JC, Soglio DB, Messinger Y, Priest JR. Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry. J Pediatr. 2006 Dec;149(6):850-854. PMID: 17137906

 Turbiner J, Amin MB, Humphrey PA, et al. (April 2007). "Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term". Am. J. Surg. Pathol. 31 (4): 489–500. doi : 10.1097/PAS.0b013e31802bdd56. PMID 17414095

 Small JE et al. Cystic Nephroma. BrighamRAD Teaching Case Database. URL: http://brighamrad.harvard.edu/Cases/bwh/hcache/385/full.html . Accessed: July 25, 2009.