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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