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Multilocular Cystic Renal Cell Carcinoma

Definition

  • Benign cystic neoplasm of the kidney composed of cysts with small groups of clear cells in the septa
    • These tumors have been named carcinomas (probably not very sensibly) because they are composed of cells indistinguishable from conventional clear cell carcinoma cells

Alternate/Historical Names

  • Multilocular renal cell carcinoma

Diagnostic Criteria

  • All of the following criteria must be met to make this diagnosis
    • Circumscribed, expansile nodule composed entirely of cysts and septa
      • Cysts are non-communicating
    • Cysts lined by single layer of low grade clear cells
      • May be largely denuded
      • No papillary growth pattern
    • Cysts separated by fibrous septa
      • May calcify or ossify
      • Lacks ovarian type cellular stroma
    • Groups of low grade clear cells are permitted within the septa
      • Must not be expansile nodules or show infiltrative growth
      • Nuclear/nucleolar grade 1 or 2
      • May exhibit increased vascularity
      • May be infrequent
      • Must be distinguished from histiocytes and lymphocytes
      • Keratin or EMA stain may aid in identification
    • The tumor must be extensively sampled to make this diagnosis
      • The presence of any expansile nodules of clear cells in the septa between the cysts indicate an ordinary, fully malignant, clear cell carcinoma with cystic change

John P Higgins MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting / updates:: 1/24/11, 12/24/12

Supplemental studies

Immunohistology

  • Keratin or EMA stain may be useful for identification of nests in septa
  • Some differences compared to usual clear cell carcinoma but they are not great enough to be useful (Williamson 2012)
    • CK7 is more frequently positive (92 vs 38%)
    • Racemase (AMACR) is less frequently positive (21 vs 67%)

Genetic Study

  • Most show 3p deletions
    • Similar to clear cell renal cell carcinoma

Differential Diagnosis

Conventional Clear Cell Renal Cell Carcinoma Multilocular Cystic Renal Cell Carcinoma
Both cystic and solid areas No solid areas
Nodules of clear cells are expansile and/or invasive Nests of clear cells are not expansile or invasive
May be low or high grade Must be low grade (1 or 2)

Multilocular Cystic Renal Cell Carcinoma Cystic Nephroma
3:1 M:F Nearly all female
Nests of clear cells in stroma No nests of clear cells in stroma
Lacks cellular ovarian type stroma Ovarian type stroma

Tubulocystic Carcinoma of the Kidney Multilocular Cystic Renal Cell Carcinoma
Lining cells have abundant eosinophilic cytoplasm Clear cells line cysts
No nests of clear cells Nests of clear cells in stroma
High grade nuclear features Low grade nuclear features

Grading / Staging

Grading

Low grade (1 or 2) by definition

  • Most commonly cited grading scheme is that of Fuhrman
    • Requires simultaneous assessment of three features: nuclear size, shape and nucleoli
      • Nuclear size may be subject to fixation variables and difficult to measure
      • No provision for cases with discrepant grade features
      • Poor interobserver agreement
  • We and others find a simplified version based primarily on nucleolar prominence to be more practical
    • This approach has been shown to have predictive value for clear cell and papillary carcinomas (Lohse; Sika-Paotonu; Delahunt)
    • Grade based on worst high powered field
    • Does not apply to chromophobe carcinoma or oncocytomas
    • Is provisionally applied to various other types and variants of RCC but has not been validated
      • Complete Fuhrman grading has not been validated on other types either
    Simplified Fuhrman Grading
    • Grade 1 Small, round, dark lymphocyte-like nuclei with without visible nucleoli
    Grade 2 Inconspicuous nucleoli, visible only at 200-400X (nuclei usually small and uniform with open, finely granular chromatin)
    Grade 3 Prominent nucleoli, easily visible at 100X (nuclei usually mildly to moderately pleomorphic)
    Grade 4 Markedly pleomorphic, bizarre nuclei, giant cells, multiple nucleoli
    • Sarcomatoid differentiation may be seen in many types of renal carcinomas (de Peralta-Venturina; Cheville)
      • It no longer refers to a type of carcinoma
      • It is considered an adverse prognostic factor
        • Prognosis may be worse than simple grade 4 carcinoma
      • Defined as a spindle cell component measuring at least one low power (40x) field with either
        • Adjacent carcinoma, or
        • Evidence of epithelial differentiation in the spindle cells
      • Spindle cells usually show moderate to marked atypia
        • Frequent patterns include fibrosarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma
        • Occasional cases have low grade atypia in spindle component
        • No clinical significance to type of differentation or degree of atypia
      • May arise in setting of many types of carcinoma
        • Clear cell RCC (reported 5-8% incidence of sarcomatoid foci, in our experience it is less frequent)
        • Papillary RCC (2-3% incidence)
        • Chromophobe RCC (9% incidence)
        • Collecting duct carcinoma (39% incidence)

    Bibliography (for Grading)

    • Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder and Related Urinary Structures, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 1, 2004
    • Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Mod Pathol. 2009 Jun;22 Suppl 2:S24-36.
    • Delahunt B, Sika-Paotonu D, Bethwaite PB, William Jordan T, Magi-Galluzzi C, Zhou M, Samaratunga H, Srigley JR. Grading of clear cell renal cell carcinoma should be based on nucleolar prominence. Am J Surg Pathol. 2011 Aug;35(8):1134-9.
    • Delahunt B, Bethwaite PB, Nacey JN. Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype. Pathology. 2007 Oct;39(5):459-65.
    • Lohse CM, Blute ML, Zincke H, Weaver AL, Cheville JC. Comparison of standardized and nonstandardized nuclear grade of renal cell carcinoma to predict outcome among 2,042 patients. Am J Clin Pathol. 2002 Dec;118(6):877-86.
    • de Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, Javidan J, Stricker H, Ro JY, Amin MB. Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases. Am J Surg Pathol. 2001 Mar;25(3):275-84.
    • Cheville JC, Lohse CM, Zincke H, Weaver AL, Leibovich BC, Frank I, Blute ML. Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome. Am J Surg Pathol. 2004 Apr;28(4):435-41.
    • Sika-Paotonu D, Bethwaite PB, McCredie MR, William Jordan T, Delahunt B. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol. 2006 Sep;30(9):1091-6.
    • Delahunt B, Sika-Paotonu D, Bethwaite PB, McCredie MR, Martignoni G, Eble JN, Jordan TW. Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Am J Surg Pathol. 2007 Jun;31(6):957-60..
    • Paner GP, Amin MB, Alvarado-Cabrero I, Young AN, Stricker HJ, Moch H, Lyles RH. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol. 2010 Sep;34(9):1233-40.
    • Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982 Oct;6(7):655-63.

    Staging

    May be staged as high as T3 based on size but no aggressive behavior reported if diagnostic criteria fulfilled

    Clinical

    • Benign if all criteria fulfilled
    • Only seen in adults
      • One reported case in an 8 year old child
        • Described as having clear cells infiltrating renal parenchyma - this feature rules out the diagnosis of multicystic renal cell carcinoma

    Classification / Lists

    Renal epithelial neoplasms

    Bibliography

    • Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder and Related Urinary Structures, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 1, 2004
    • Eble JN, Sauter G, Epstein JI, Sesterhenn IA eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the Urinary System and Male Genital Organs. IARC Press: Lyon 2004.
    • Störkel S, Eble JN, Adlakha K, Amin M, Blute ML, Bostwick DG, Darson M, Delahunt B, Iczkowski K. Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer. 1997 Sep 1;80(5):987-9.
    • Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, Ritz E, Roos G, Schmidt D, Srigley JR, Störkel S, van den Berg E, Zbar B. The Heidelberg classification of renal cell tumours. J Pathol. 1997 Oct;183(2):131-3.
    • Moch H. Cystic renal tumors: new entities and novel concepts. Adv Anat Pathol. 2010 May;17(3):209-14.
    • Halat S, Eble JN, Grignon DJ, Lopez-Beltran A, Montironi R, Tan PH, Wang M, Zhang S, MacLennan GT, Cheng L. Multilocular cystic renal cell carcinoma is a subtype of clear cell renal cell carcinoma. Mod Pathol. 2010 Jul;23(7):931-6.
    • Gong K, Zhang N, He Z, Zhou L, Lin G, Na Y. Multilocular cystic renal cell carcinoma: an experience of clinical management for 31 cases. J Cancer Res Clin Oncol. 2008 Apr;134(4):433-7.
    • Suzigan S, López-Beltrán A, Montironi R, Drut R, Romero A, Hayashi T, Gentili AL, Fonseca PS, deTorres I, Billis A, Japp LC, Bollito E, Algaba F, Requena-Tapias MJ. Multilocular cystic renal cell carcinoma : a report of 45 cases of a kidney tumor of low malignant potential. Am J Clin Pathol. 2006 Feb;125(2):217-22.
    • Menon P, Rao KL, Kakkar N, Saxena AK, Singh M. Multilocular cystic renal cell carcinoma in a child. J Pediatr Surg. 2004 Oct;39(10):e14-6. (Note: the clear cells are described as infiltrating the renal parenchyma - this is not multilocular cystic renal cell carcinoma. (rvr))
    • Williamson SR,  Halat S,  Eble JN,  Grignon DJ,  Lopez-Beltran A, Montironi R,  Tan P-H,  Wang M,  Zhang S, MacLennan GT,;  Baldridge LA,  Cheng L. Multilocular cystic renal cell carcinoma: similarities and differences in immunoprofile compared with clear cell renal cell carcinoma. American Journal of Surgical Pathology 36(10):1425-1433, October 2012.
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