Cystic Nephroma/Mixed Epithelial and Stromal Tumor

Cystic Nephroma/Mixed Epithelial and Stromal Tumor
Satish K. Tickoo, MD
Victor E. Reuter, MD
Key Facts
Terminology
  • Cystic nephroma (CN), mixed epithelial and stromal tumor (MEST)
  • Multicystic to solid and cystic biphasic renal tumors that likely represent morphologic spectrum of same entity
Clinical Issues
  • CN: F:M = approximately 8:1; MEST: Mostly in females with only rare reported cases in males
  • Incidentally detected kidney mass is most common clinical presentation
  • All reported cases of typical CN and MEST have behaved in benign fashion following surgical excision
Macroscopic Features
  • CN: All tumors entirely cystic with no solid areas or expansile nodules
  • MEST: Variably solid and cystic, sometimes with predominant solid component
Microscopic Pathology
  • Stroma in both CN and MEST with varied histologic features
  • Epithelial components in both CN and MEST with varied but similar features
Top Differential Diagnoses
  • Multilocular cystic RCC, tubulocystic carcinoma, CPDN, mesoblastic nephroma (classical type), metanephric adenofibroma
Gross photograph of a cystic nephroma shows an exclusively cystic, well-circumscribed tumor with no solid areas. Gross distinction from multilocular cystic RCC is not possible in such cases.
Gross appearance of a mixed epithelial and stromal tumor shows a predominantly solid morphology. Relatively few cysts image are apparent on gross evaluation.
TERMINOLOGY
Abbreviations
  • Cystic nephroma (CN), mixed epithelial and stromal tumor (MEST)
Synonyms
  • Renal epithelial and stromal tumor (REST)
  • For MEST: Adult mesoblastic nephroma, cystic hamartoma of renal pelvis, leiomyomatous renal hamartoma, or solid and cystic biphasic tumor
Definitions
  • Multicystic to solid and cystic, mostly benign, biphasic renal tumors that likely represent morphologic spectrum of same entity
  • CN: Tumor composed entirely of cysts and cyst septae without any solid expansile areas or mural nodules
    • Septations with arbitrarily chosen thickness of less than 5 mm
  • MEST: Tumors with variable amounts of solid components
ETIOLOGY/PATHOGENESIS
Role of Hormones
  • Features that suggest role of steroid hormones in genesis and evolution of these tumors include
    • Marked female preponderance
    • Common history of long-term estrogen replacement in female patients
    • Long-term sex steroid exposure in male patients
    • Frequent expression of ER and PR in tumor mesenchymal component
Genetic Alterations
  • Gene expression profiles of mRNA demonstrate that both CN and MEST share similar expression profiles
    • Highest differentially expressed gene, relative to other tumors and nonneoplastic parenchyma, is insulin-like growth factor 2
    • Lowest differential expression is of carbonic anhydrase 2 gene
  • Single case of translocation t(1;19) in MEST also reported
CLINICAL ISSUES
Epidemiology
  • Age
    • Mean age similar for both CN and MEST: Approximately 53 years (range: 34-78 years)
    • CN in pediatric age group considered to be fully differentiated nephroblastoma
      • Not related to tumors seen in adults
  • Gender
    • CN: F:M approximately 8:1
    • MEST: Mostly in females with only rare reported cases in males
Presentation
  • Incidentally detected kidney mass is most common clinical presentation
  • Other described symptoms
    • Abdominal pain
    • Hematuria
    • Urinary tract infections
Prognosis
  • All reported cases of typical CN and MEST have behaved in benign fashion following surgical excision
    • 1 reported case of MEST recurred locally 21 years after resection
  • A few cases of malignant MEST reported in literature
    • Malignant phenotype observed in either epithelial or mesenchymal components
      • Morphologic features of malignancy include increased cellularity, cytologic atypia, prominent nucleoli, and high mitotic rate
    • Spindle cell NOS, synovial sarcoma, rhabdoid, rhabdomyosarcoma, and chondrosarcoma differentiation in malignant stromal components
MACROSCOPIC FEATURES
General Features
  • Cystic nephroma
    • Tumors usually solitary; very rare bilateral cases reported
    • Most tumors well circumscribed and confined to kidney
    • Located mostly close to renal hilum but may involve cortex, particularly in larger tumors
    • All tumors entirely cystic with no solid areas or expansile nodules
      • Majority of cysts contain clear serous fluid, rarely hemorrhagic or purulent material
  • Mixed epithelial and stromal tumor
    • Mostly solitary and unilateral, with rare bilateral cases
    • Most tumors well circumscribed and confined to kidney
      • Very few tumors with ill-defined, infiltrative borders
    • Located mostly close to renal hilum and renal pelvis but may involve cortex, particularly in larger tumors
    • Variably solid and cystic, sometimes with predominant solid component
Size
  • Size range similar for both CN and MEST: 1.7-21 cm (mean: 6.5 cm)
MICROSCOPIC PATHOLOGY
Histologic Features
  • Stroma in both CN and MEST show varied histologic features, including
    • Loose fibrous and edematous
    • Dense fibrous and sclerotic
    • Hypercellular spindled, NOS
    • Ovarian stroma-like
    • Smooth muscle type
  • Prominent vasculature more common in MEST
  • Calcifications and foamy histiocytes present in both CN and MEST
  • Cells in epithelial components in both CN and MEST show varied features, including
    • Flat
    • Hobnailed
    • Cuboidal
    • Columnar
    • Urothelial-like
    • Clear cell
    • However, clear cell or urothelial-like cyst lining relatively uncommon in CN
  • Prominent ovarian stroma, smaller cysts, complex branching glands, phyllodes gland pattern, and stromal luteinization more common in MEST than CN
Predominant Pattern/Injury Type
  • Neoplastic
Predominant Cell/Compartment Type
  • Epithelial, biphasic or mixed
ANCILLARY TESTS
Immunohistochemistry
  • Stromal cells often positive for ER, PR, and less commonly for inhibin and calretinin, in both (but more often in MEST)
DIFFERENTIAL DIAGNOSIS
Multilocular Cystic Renal Cell Carcinoma
  • Differentiation is required from CN and predominantly cystic MEST
    • Multilocular cystic RCC with cysts showing variable flattened lining or almost entirely larger cells with clear cytoplasm
    • Clusters or nests of clear cells are always present in septae
    • No cellular or ovarian-type stroma
    • Lining cells with a CA9, CD10, and often CK7 positive immunophenotype
    • No stromal immunoreactivity for ER and PR
Tubulocystic Carcinoma
  • Tubulocystic carcinoma needs to be differentiated from CN and predominantly cystic MEST
    • Cells lining tubules and cysts in tubulocystic carcinoma have high-grade nuclei and abundant eosinophilic cytoplasm
    • Stroma usually dense fibrotic and desmoplastic
    • Septae often incomplete and free floating
    • No ER and PR positivity
Cystic Partially Differentiated Nephroblastoma (CPDN)
  • CPDN needs to be differentiated from CN and predominantly cystic MEST
    • CPDN shows at least focal nephroblastematous tissue, such as blastema, immature stromal cells, and primitive epithelium in septae
    • Almost all patients < 24 months old
Mesoblastic Nephroma (Classical Type)
  • Differential is with solid MEST
    • Classical mesoblastic nephroma shows finger-like extensions into surrounding renal parenchyma
    • Entrapped native tubules and glomeruli are often seen in mesoblastic nephroma
      • However, these are seen almost entirely in periphery of tumor
    • Mesoblastic nephroma shows no ER or PR positivity
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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cystic Nephroma/Mixed Epithelial and Stromal Tumor

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