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2012 — April Case of the Month

Posted April 17, 2012

CLINICAL SUMMARY: Kidney  

CAP Foundation April Online Case of the Month

Click Slide Image to View Case with DigitalScope

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

A 48-year-old woman presented with flank pain. Imaging studies revealed a multicystic lesion of the right kidney suspicious for renal cell carcinoma. A nephrectomy was performed. The resected 754 g kidney contained a 12.5 x 12.0 x 9.0 cm multiloculated cystic mass with focal white solid nodules, grossly abutting the renal pelvis but apparently confined to the kidney.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2009, case 13, and is mixed epithelial and stromal tumor.

Criteria for Diagnosis and Comments:
The distributed sections show multiple cysts lined by attenuated to cuboidal epithelium with bland nuclei. Occasionally hobnail cells are noted. The cysts are separated by stroma, which is variably collagenous and ovarian-like with interspersed thick walled blood vessels. The combined clinical, morphologic, and immunohistochemical findings are most compatible with a mixed epithelial and stromal tumor of the kidney (MEST).

MEST is a benign neoplasm previously described as adult mesoblastic nephroma and cystic hamartoma of the renal pelvis. This lesion occurs almost exclusively in perimenopausal women, many of whom have a history of prolonged estrogen use. Most are discovered incidentally in imaging studies performed for another complaint; however, some patients do present with symptoms, most commonly hematuria, flank pain, or urinary tract infections. MEST is typically solitary, centered on the renal pelvis, well circumscribed, and confined to the kidney. The macroscopic appearance is distinctive, with multiple cysts, small and large, separated by tan, fleshy to yellow-white solid stromal nodules. Microscopically, the cysts in MEST are lined by cuboidal, flattened or, more commonly, hobnail epithelium with amphophilic, and rarely clear, cytoplasm. Occasionally the epithelium may be columnar, ciliated, or urothelial-like. Rarely, reactive epithelial atypia is observed; however, significant pleomorphism and mitotic activity are lacking. The spindle cell stromal component may be paucicellular and collagenous or cellular with a fascicular pattern. When well sampled, virtually all lesions will contain ovarian-like stroma. The more cellular lesions may appear leiomyomatous. Some lesions will show alternating zones of high and low cellularity with eosinophilic collagen bundles, as seen in solitary fibrous tumor. Thick-walled blood vessels, myxoid change, fat cells, and stromal edema may all be observed; blastema, immature mesenchymal tissue, mitotic activity and necrosis are absent. A significant minority of MEST exhibit condensation of the stroma around branching epithelial structures, closely resembling phyllodes tumor of the breast.

The immunohistochemical profile of these neoplasms is distinctive. The stromal cells are variably immunoreactive for smooth muscle actin, desmin, estrogen receptor, progesterone receptor, and CD10. The latter three markers are most commonly observed in the ovarian-like stroma, which may also exhibit immunoreactivity for calretinin and inhibin, reflecting luteinization of the stromal cells. Recently, a PEComatous variant has been described in which HMB-45 positivity is present in a subset of the smooth muscle actin positive myoid stromal cells. The epithelial component uniformly expresses keratin and vimentin with a subset showing immunoreactivity for CD10 in a brush border pattern; the morphologically Mullerian type epithelium may be positive for estrogen and progesterone receptors.

It is postulated that MEST arises from periductal fetal mesenchyme or through the abnormal migration of ovarian stroma during embryogenesis. This tissue has the potential to proliferate in a state of hormonal imbalance (menopause, unopposed estrogen use) and induce the development of a closely apposed epithelial component. Some authors have further suggested that there is a link between MEST and similar mucinous cystic neoplasms with ovarian-like stroma in the liver and pancreas. These histogenetic hypotheses are supported by the clinical presentation of this neoplasm and the presence of estrogen and progesterone receptor expression in stromal cells.

The clinical behavior of MEST is virtually always benign although recurrences have been described and there have been rare reports documenting malignant transformation of the stromal component. The principal differential diagnosis of MEST is with other cystic neoplasms of the kidney: cystic nephroma (CN), cystic partially differentiated nephroblastoma (CPDN) and multilocular cystic renal cell carcinoma (MCRCC). Although cystic nephroma does not exhibit the architectural complexity of cysts and glands, or the complex branching, columnar, clear and urothelial-like epithelium that may be seen in MEST, CN shows significant clinical and morphologic overlap with MEST; recently it has been suggested that CN and MEST represent two ends of a histologic spectrum and should be combined into a single entity – renal epithelial stromal tumor (REST). This proposal is supported by molecular data showing that the mRNA profile of these two tumors is similar and distinct from other renal neoplasms. However, in the current WHO classification the two neoplasms remain separate entities with CN defined by a predominance of cysts and, by arbitrary definition, stromal septa that are no greater than 5 mm in thickness.

CPDN is a distinctive variant of nephroblastoma, which like all nephroblastomas, is a lesion of children, most less than 2 years old. Adult CPDN has been described; however, these lesions are generally thought to be MEST. In contrast to CPDN, blastema, undifferentiated mesenchyme, and nephroblastic epithelium have not been described in MEST. MCRCC shows cysts lined by epithelium with clear cytoplasm and thin fibrous septa; in cases with attenuated or absent epithelium, these tumors may mimic MEST. In contrast to MEST, however, on careful sampling, nodules of cytologically atypical clear cells are found within the fibrous septa. Metanephric adenofibroma, a rare biphasic tumor of children and young adults, is easily distinguished from MEST by clinical features, by the paucity of cysts, and by the presence of a characteristic metanephric-adenoma like epithelial component. Angiomyolipoma and solitary fibrous tumor would enter the differential diagnosis only in very rare cases of non-cystic MEST; in these cases careful sampling will disclose the epithelial component of MEST. In difficult cases, immunohistochemistry for HMB-45 and CD34, both characteristically absent in MEST (with the exception of the above-mentioned PEComatous variant), may be of utility.

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 tumor shows significant clinical and histologic overlap with cystic nephroma? A. Angiomyolipoma
B. Cystic partially differentiated nephroblastoma
C. Metanephric adenofibroma
D. Mixed epithelial and stromal tumor
E. Multilocular cystic renal cell carcinoma
F. Solitary fibrous tumor
2. Which tumor is seen predominantly in children under the age of 2? A. Angiomyolipoma
B. Cystic partially differentiated nephroblastoma
C. Metanephric adenofibroma
D. Mixed epithelial and stromal tumor
E. Multilocular cystic renal cell carcinoma
F. Solitary fibrous tumor
3. Which tumor is characterized by cysts lined by flattened, cuboidal or hobnail epithelium and septa containing ovarian-like stroma? A. Angiomyolipoma
B. Cystic partially differentiated nephroblastoma
C. Metanephric adenofibroma
D. Mixed epithelial and stromal tumor
E. Multilocular cystic renal cell carcinoma
F. Solitary fibrous tumor

References

  1. Adsay NV, Eble JN, Srigley JR, et al. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol. 2000;24:958-970.
  2. Antic T, Perry KT, Harrison K, et al. Mixed epithelial and stromal tumor of the kidney and cystic nephromas share overlapping features: reappraisal of 15 lesions. Arch Pathol Lab Med. 2006;130:80-85.
  3. Eble JN, Bonsib SM. Extensively cystic renal neoplasms: cystic nephroma, partially differentiated nephroblastoma, multilocular cystic renal cell carcinoma and cystic hamartoma of renal pelvis. Semin Diagn Pathol. 1998;15:2-20.
  4. Eble JN. Mixed epithelial and stromal tumor. In: Eble JN, Sauter G, Epstein JI. WHO Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC Press; 2004:77-78.
  5. Jung SJ, Shen SS, Tran T, et al. Mixed epithelial and stromal tumor of the kidney with malignant transformation: report of two cases and review of the literature. Hum Pathol. 2008;39:463-468.
  6. Mai KT, Elkeilani A, Veinot JP. Mixed epithelial and stromal tumour (MEST) of the kidney: Report of 14 cases with male and PEComatous variants and proposed histopathogenesis. Pathology. 2007;39:235-240.
  7. Michal M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract. 1998;194:445-448.
  8. Michal M, Hes O, Bisceglia M, et al. Mixed epithelial and stromal tumors of the kidney. A report of 22 cases. Virchows Arch. 2004;445:359-367.
  9. Truong LD, Choi YJ, Shen SS, et al. Renal cystic neoplasms and renal neoplasms associated with cystic renal diseases: Pathogenesis and molecular links. Adv Anat Pathol. 2003;10:135-159.
  10. Turbiner J, Amin MB, Humphrey PA, et al. Cystic nephroma and mixed epithelial and stromal tumor of the 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. 2007;31:489-500.
  11. Zhou M, Kort E, Hoekstra P, et al. Adult cystic nephroma and mixed epithelial and stromal tumor of the kidney are the same disease entity: Molecular and histologic evidence. Am J Surg Pathol. 2009;33:72-80.

Author:
2008
Richard W. Brown, MD FCAP
Surgical Pathology Committee
Memorial Hermann Healthcare System,
Houston, TX