—  SPECIALTY CONFERENCE  —

SURGICAL PATHOLOGY

Case 3 - Mixed Epithelial and Stromal Tumor of the Kidney (MESTK)

Michal Michal, M.D.
Medical Faculty Hospital
Pilsen, Czech Republic

Clinical History:
A 48 year-old woman was seen for flank pain and a right abdominal mass. A right kidney tmnor was excised. The resected kidney measured 16x14x12 cm. The tumor was localized in the central part of the kidney. It was 10 cm in diameter, round, well circumscribed with a thin fibrous capsule. There were no signs of infiltrative growth into the surrounding renal parenchyma. The tumor was situated within the renal parenchyma and compressed the adjacent calyceal system. Grossly the tumor had a solid appearance without cyst formation, with a white cut surface, and soft to elastic consistency without hemorrhage or necrosis.

Histologic Findings:
The tumor had distinct adenomatous and mesenchymal components. The adenomatous component consisted of variously sized ducts, which ranged from very minute, ductuli with a thick basal membrane to larger ducts with well formed lumina. The largest ducts contained cells with "hobnail" appearance. The cytoplasm of the cells in the ducts stained deeply red with H&E stain. The duct contained PAS and Alcian Blue positive and mucicarmine negative secretion and the cytoplasm of the cells of the adenomatous component was often deeply eosinophilic. The adenomatous component was surrounded by a spindled mesenchymal stroma. The spindle cells closely resembled ovarian stroma. Sparse small lymphocytes were also present in the stroma. This ovarian-like stroma suuounded clusters of small neoplastic ductules or grew among the larger ducts. The stroma was always centered on the adenomatous component and never formed compact sheets devoid of adenomatous elements. In spite of the similarity of the mesenchymal component to the ovarian stroma, follicle-like structures, specialized gonadal stromal structures or luteinization characteristic of the ovary was absent. No immature embryonal renal tissue, papillary epithelial differentiation, transitional urothelial epithelimn or stromal heterologous cellular structures were present in the tumor. No mitoses, atypia, hemorrhage, necrosis or foci of extramedullary hematopoiesis were observed. A pararenal lymph node, which was excised together with the right kidney, had a normal structure and was negative for tumor. Immunohistochemically, the epithelial elements reacted with antibodies to cytokeratins and were negative with antibodies to synaptophysin, serotonin and chromogranin. The eosinophilic cells in the ducts stained strongly with antibody to mitochondrial antigen 113-1. Antibodies to EMA and CEA were positive only in the secretory elements and the superficial glycocalyx of the ducts. The cytoplasm of the neoplastic cells was negative. The spindle stromal cells were positive with antibodies to muscle actin, smooth muscle actin, CD34 and desmin (clone D33). Antibody to MIB1 reacted only in less then 1% of the epithelial and stromal cells revealing thus a very low level of the cell proliferation in the tumor.

Slides  (Click to enlarge)


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The tumor is composed of adenomatous and mesenchymal components. The adenomatous component shows variously sized ductules and ducts with flattened to euboidal cells with a "hobnail" appearance. There is a spindled mesenchymal component. The tumor is composed of numerous small ductules and a spindled mesenchymal stroma. The tumor is composed of numerous small ductules and a spindled mesenchymal stromal component. The tumor contains many small ductules or tubules and the spindled mesenchymal component. Immuno-
cytochemistry for cytokeratin (AE1/AE3). There is intense staining of the cytoplasm of the cells lining the ductules/tubular structures of this tumor.

Diagnosis: Mixed epithelial and stromal tumor of the kidney (MESTK)

Comment:
MESTK was first desclibed by Michal and Syrucek in 199814 as a renal counterpart of pancreatic and biliary cystadenomatous neoplasms containing ovarian-like stroma.6,8 Two years later, in the April issue of Pathology Research and Practice, Michal widened the concept of MESTK, unifying several hitherto variously designated neoplasms into one distinct entity. These renal tumors were previously designated as adult type mesoblastic nephroma,19 cystic hamartoma of the pelvis,13,16 adult type of cystic nephroma,9,12 multilocular renal cysts5,7,10 and solid and cystic biphasic tumor of the kidney.1,17 The designation of benign mixed epithelial and stromal tumor of the kidney (MESTK) was proposed as a unifying term for all of them.15

Histologically, all these tumors resemble each other far more than they differ from one another. The main differences among these tumors are in the relative amount and configuration of their epithelial component, cellularity and the tumor localization. It seems that when the epithelial component of these tumors is cystically dilated, they were called cystic nephromas (in adults);9 when the epithelial component was partly cystic and partly solid, they were called solid and cystic biphasic tumors of the kidney1,17 or mesoblastic nephromas in adults;19 and when the tumors were located predominantly in the pelvis they were called cystic hamartomas of the pelvis.13,16

Their common histologic and clinical features include: 1) They nearly exclusively occur in middle aged to older women, 2) the stroma has the morphology and immunohistochemical properties of ovarian stroma; and 3) there is always a variably cystic epithelial component with eosinophilic cytoplasm and often hobnail appearance (similar to collecting ducts).

In the July issue of the American Journal of Surgical Pathology the same year (2000), Adsay et al presented a practically identical concept for these lesions and expanded the list of tumors previously published under different names that could fit into the MESTK concept. They further proved that these tumors often express estrogen/progesterone receptors. Interestingly, the only male patient in their series of 12 cases had a 7-year history of diethylstilbestrol therapy followed by 4 years of lupron for prostatic adenocarcinoma.1 Beiko et al published a case of MESTK of possible Mullerian origin.4 Svec et al reported a synovial sarcoma arising in MESTK.18 In addition to this reported case, we have seen two cases of synovial sarcomas of the kidney arising in MESTK. It thus seems that a considerable part of synovial sarcomas arising in the kidney may have origin in MESTK.3,11

References

  1. Adsay V, Eble JN, Srigley JR, Jones EJ, Grignon DJ. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 2000:24:958-970
  2. Adsay V, Grignon D, Eble J, Jones E. Solid and cystic biphasic tumor of the adult kidney. Mod Pathol 1998:11: 74A
  3. Argani P, Faria P A, Epstein J I, Reuter VE, Perlman EJ, Beckwith JB, Ladanyi M (2000) Primary renal synovial sarcoma. Molecular and morphologic delineation of an entity previously included among embryonal sarcomas of the kidney. Am J Surg Pathol 24: 1087-1096
  4. Beiko DT, Nickel JC, Boag AH, Srigley JR. Benign mixed epithelial stromal tumor of the kidney of possible Mullerian origin. J Urol 2001:166:1381-1382
  5. Bennington Jl, Beckwith JB (1975) Atlas of Tumor Pathology; Tumors of the Kidney, Renal Pelvis, and Ureter. Second Series, Fascicle 12, Reprinted 1983, pp 84-85, Armed Forces Institute of Pathology, Washington, D.C.
  6. Compagno J, Oertel JE. Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Pathol 1978:69:573-580
  7. Davila RM, Kissane JM, Crouch EC. Multilocular renal cyst. Immunohistochemical and lectin-binding study. Am J Surg Pathol 1992:16:508-514
  8. Devaney K, Goodman ZD, Ishak KG. Hepatobiliary cystadenoma and cystadenocarcinoma. A light microscopic and immunohistochemical study of 70 patients. Am J Surg Pathol 1994:18:1078-109l
  9. Eble JN, Bonsib SM. Extensively cystic renal neoplasms: cystic nephroma, cystic partially differentiated nephroblastoma, multilocular cystic renal cell carcinoma, and cystic hamartoma of renal pelvis. Semin Diagn Pathol 1998:15:2-20
  10. Joshi VV , Beckwith JB. Multilocular cyst of the kidney (cystic nephroma) and cystic, partially differentiated nephroblastoma. Cancer 1989:64:466-479
  11. Kim DH, Sohn JH, Lee MC, Lee G, Yoon GS, Hashimoto H, Sonobe H, Ro JY (2000) Primary synovial sarcoma of the kidney. Am J Surg Pathol 24: 1097-1104
  12. Madewell JE, Goldman SM, Davis CJ, Hartman DS, Feigin DS, Lichtenstein JE Multilocular cystic nephroma. A radiographic-pathologic correlation of 58 patients. Radiology 1983:146:309-321
  13. Mensch LS, Trainer TD, Plante MK. Cystic hamartoma of the pelvis: a rare pathologic entity. Mod Pathol 1999:12:417-421
  14. Michal M, Syrucek M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract 1998:194:445-448
  15. Michal M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract 2000:196:275-276
  16. Pawade J, Soosay GN, Delprado W, Parkinson MC, Rode J. Cystic hamartoma of the renal pelvis. Am J Surg Pathol 1993:17: 1169-1175
  17. Pierson C, Wallis T, Eble J, Srigley J, Jones E, Grignon D, Adsay V. Solid and cystic biphasic tumor of the kidney lacks cytogenetic abnormalities typical of mesoblastic nephroma. Mod Pathol 1999:12:104A
  18. Svec A., Michal M. Malignant mixed epithelial and stromal tumor of the kidney. Virchows Archiv, 2001:439:700-702
  19. Truong LD, Williams R, Ngo T, Cawood C, Chevez-Barrios P, AwaIt HL, Brown RW, Younes M, Ro JY (1998) Adult mesoblastic nephroma. Expansion of the morphologic spectrum and review of literature. Am J Surg Pathol 22: 827-839