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2009 — May Case of the Month

Updated April 29, 2009

CLINICAL SUMMARY: KIDNEY  

CAP Foundation May 2009 Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 2-year-old boy presented with a distended abdomen and was discovered to have a right-sided abdominal mass. Following appropriate workup, a renal tumor was removed. A 13.0 x 11.0 x 9.0 cm, 810.0 gm right kidney and adrenal gland was submitted for examination. Cut surfaces demonstrated that the kidney was virtually replaced by a variegated and focally necrotic tumor, which was confined to the kidney by an intact capsule. Sections of tumor extending into the renal hilum exhibited tumor invading lymphatics and venules in the soft tissues supporting renal calyces.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2006, Case 12 and is a Wilms tumor.

Criteria for Diagnosis and Comments:
Most sections revealed a triphasic (stromal, blastemal and epithelial component) Wilms tumor. The remainder was blastema predominant Wilms tumor lacking an epithelial or stromal component. Anaplasia was absent.

Unlike neuroblastoma, where histology, stage, age and MYC N expression are important prognostic factors, the most important prognostic features of primary childhood renal tumors are histology and stage alone.

The three most frequent primary renal tumors of children after Wilms tumor (congenital mesoblastic nephroma, clear cell sarcoma and malignant rhabdoid tumor) are easily distinguished from Wilms tumor.

By far the most benign of childhood renal tumors, the congenital mesoblastic nephroma is a uniform spindle cell lesion that may contain macro or microcysts. The latter probably originate from nephrons obstructed by the diffusely infiltrating tumor. Mitoses are usually uncommon, but the more cellular variant may be quite mitotic and resemble a congential fibrosarcoma both phenotypically and genotypically with a t (12;15).

Clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumor of the kidney (MRTK) are distinctive, highly aggressive tumors not related to Wilms tumors. Neither occurs in combination with Wilms tumor. CCSK may have as many as 5 histologic patterns but none resembling Wilms tumor blastema. All CCSK patterns have round to spindled nuclei with delicate nucleoli associated with variable optically clear cytoplasm, supported by a stroma comprising a prominent arborizing capillary network. Light microscopic, ultrastructural and immunophenotypic epithelial differentiation is absent in CCSK. Of note, many slides in the present case may have spindled blastema in addition to islands of small round cell blastema, suggesting the joint occurrence of clear cell sarcoma of the kidney (CCSK) and Wilms tumor. However, as stated, this combination never occurs.

MRTK comprises cells with prominent eosinophilic cytoplasm and eccentric nuclei with prominent nucleoli resembling rhabdomyoblasts. The term "rhabdoid" was coined to indicate "rhabdomyoblast-like". While lacking immunophenotypic features of rhabdomyoblasts, MRTK cells react with antibodies to epithelial and mesenchymal epitopes.

Unlike Wilms tumor, CCSK has a tendency to metastasize to bone and MRTK has a documented association with a cerebral PNET that may exhibit rhabdoid features, the so-called atypical teratoid rhabdoid tumor.

Wilms tumor (nephroblastoma) is the most common genitourinary tumor of childhood. It most frequently occurs between the ages of 1 and 3 years. The classic (triphasic) Wilms' tumor exhibits epithelial, stromal, and blastemal expression. Blastema, resembling the condensed mesenchyme from which the kidney develops, is usually present in Wilms tumors. Blastemal predominance is a term used to indicate that blastema comprises more than 33% of the tumor. Blastema may be the only element in a Wilms tumor. If blastema lacks a familiar serpentine or nodular pattern but is instead diffuse sheets of mitotically active small round cells lacking stromal or epithelial differentiation, it must be distinguished from other small blue cell tumors.

The monotonous small round cell appearance of blastemal cells in a Wilms tumor comprised of blastema alone may mimic poorly differentiated neuroblastoma and peripheral primitive neuroectodermal tumor (PNET). Immunocytochemistry and/or electron microscopy may be required to distinguish blastemal Wilms from other small blue cell tumors. While both Wilms blastema and PNET will express vimentin and may express cytokeratin, blastema does not express MIC2 gene product (CD 99) in the experience of the National Wilms Tumor Study Group (NWTS) Pathology Center. Distinction of primitive neuroblastoma or PNET from Wilms blastema by immunocytochemistry may be complicated by the fact that blastemal small round cells will occasionally bind antibodies to synaptophysin. In this situation, electron microscopic examination will exhibit either characteristic features of neuroblastoma or the layer of thick flocculent electron dense material adhering to blastemal external cell surfaces.

While presenting a diagnostic dilemma, a purely blastemal presentation does not signify a different prognosis from other patterns of Wilms tumor. The most important prognostic features are stage and the presence or absence of cellular anaplasia in the blastemal or epithelial compartments. Anaplasia distinguishes the tumor as having "unfavorable" histology and signifies resistance to drug therapy. In the absence of anaplasia, Wilms histology is termed "favorable".

The prognostic significance of staging is demonstrated in multiple National Wilms Tumor Studies. A stage I tumor is confined to the kidney. Tumor bulging into the hilum of the kidney does not "up-stage" the tumor to stage II unless it exhibits microscopic lymphovascular invasion. Thus, this case is a stage II tumor. A stage III designation is assigned when tumor directly extends to other abdominal structures or is identified in abdominal lymph nodes. Hematogenous metastases establish a stage IV tumor. Bilateral Wilms tumors signify a stage V category.

The majority of nephroblastomas are low stage at presentation, exhibit "favorable" histology and have an excellent prognosis following conventional chemotherapy.

Supplementary Questions For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which are the most important prognostic features of Wilms tumor? A. Stage
B. Histology
C. Age and MYC N expression
D. A & B
E. A, B and C
2. Which of the following antigens may react in Wilms tumor? A. Vimentin and perhaps cytokeratin
B. Vimentin, cytokeratin and EMA
C. NSE and synaptophysin
D. CD 99
E. None of the above
3. Which of the following tumors are likely to be considered in the differential diagnosis of blastemal-rich Wilms tumor? A.  Primary renal neuroblastoma and Peripheral primitive neuroectodermal tumor (PNET).
B. Malignant rhabdoid tumor of kidney
C. Clear cell sarcoma of kidney
D. Congenital mesoblastic nephroma
E. B, C and D

References

  1. Argani P, Perlman EJ, Breslow NE, et al. Clear Cell Sarcoma of the Kidney. A Review of 351 Cases From the National Wilms Tumor Study Group Pathology Center. Am J Surg Pathol. 2000;24:4-18.
  2. Eble JN, Young RH. Tumors of the urinary tract. In: Fletcher CDM, ed. Diagnostic Histopathology of Tumors, 2nded. New York, NY, Churchill Livingstone; 2000:502-512.
  3. Husain AN, Pysher TJ, Dehner LP. In: Stocker JT, Dehner LP, ed. Pediatric Pathology. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:874-884.
  4. Mierau GW, Weeks DA, Hicks MJ. Role of electron microscopy and other special techniques in the diagnosis of childhood round cell tumors. Hum Pathol. 1998;29:1347-1355.
  5. Murphy WM, Beckwith JB, Farrow GM. In Tumors of the Kidney, Bladder and Related Urinary Structures. Atlas of Tumor Pathology. 3rd Series, Fascicle 11. Washington DC: Armed Forces Institute of Pathology; 1994:12-89.
Author:
2006
Joel E. Haas, MD
Surgical Pathology Committee
The Children's Hospital
Denver, CO