Renal mixed epithelial and stromal tumor : case report Tumor epitelial-estromal misto do rim : relato de caso

Mixed epithelial and stromal tumor (MEST) represents a recently described biphasic kidney neoplasm, which predominantly affects perimenopausal females. The authors report the case of a young male patient with a MEST exhibiting positivity for estrogen and progesterone receptors. Computed tomography/magnetic resonance imaging (CT/MRI) showed an expansive lesion affecting the right kidney. Grossly, a solid-cystic tumor was identified, which measured 5.7 × 3.5 × 2.4 cm. On microscopic examination, a biphasic tumor constituted by stromal and epithelial elements, without significant atypias, was identified. The stromal element was composed of spindle cells revealing positive immunoexpression for actin, desmin, vimentin, and estrogen receptors. The epithelial component exhibited a predominantly tubular pattern showing positive immunoreaction for cytokeratins. The diagnosis of MEST was then established.


intRoDuCtion
Tumors of the kidney amount to 2% of the total human cancer burden, and renal cell carcinoma represents, on average, over 90% of all malignances of the kidney.Mixed epithelial and stromal tumor (MEST) is a complex renal neoplasm composed of a mixture of stromal and epithelial elements (1)(2)(3) .These rare lesions have been termed cystic hamartoma of renal pelvis, adult mesoblastic nephroma, leiomyomatous renal hamartoma, and mesoblastic nephroma (1,(4)(5)(6) .MEST is four to six times more common in women than in men.All patients have been adults, with a mean age of 46 years.Owing to the disparity between incidence rates in women and men, a hormonal influence on the development of MEST has been suggested (1)(2)(3)6) . Heren the authors report the case of a male patient with a MEST exhibiting positive immunoexpression of estrogen and progesterone receptors, and discuss clinical and morphologic findings of this uncommon tumor.

CaSE REPoRt
A 26-year-old male patient was admitted to the nephrology service due to a 30-day history of macroscopic hematuria episodes.On physical examination, there were no clinical changes.There was no previous history of relevant disease.On laboratory investigation, glucose, hemoglobin, erythrocytes, creatinine, urea, liver enzymes, and cholesterol were within normal plasma levels.Serologic tests for hepatitis B virus, hepatitis C, and HIV were negative.Qualitative urinalysis revealed the presence of several red blood cells per field.Abdominal computed tomography/ magnetic resonance imaging (CT/MRI) showed an expansive round lesion affecting the inferior pole of the right kidney.CT/ MRI of the chest has not identified significant alterations.The patient underwent radical nephrectomy.On gross examination, an ovoid well-circumscribed solid-cystic pale tumor was identified, which measured 5.7 × 3.5 × 2.4 cm (Figure 1).The process did not compromise the renal capsule or the perinephric tissues.
On microscopic examination, a biphasic tumor was found.The stromal element was composed of spindle cells arranged in short fascicles (Figure 2), and varying from hypocellular to fibrotic areas.The epithelial element was constituted by cuboidal to columnar cells showing clear or acidophilic cytoplasm and ovoid central nuclei.Epithelial cells were distributed in immature tubules exhibiting various degrees of luminal dilation, and/or forming micro-and macrocysts.Neither significant atypia nor necrosis was identified.The stromal element exhibited positive immunoexpression for actin, desmin, vimentin, and estrogen (Figure 3) and progesterone receptors.The epithelial component showed positive immunoreactions for cytokeratins (AE1/AE3) and vimentin.The tumor exhibited negative immunoexpression for melanocyte antigen (melan-A), and human melanoma black 45 (HMB-45).The diagnosis of kidney MEST was then established.

DiSCuSSion
MEST comprises a rare tumor of the kidney that is more common in women than in men (6:1, respectively).In general, patients are adults, with a mean age of 45 years.MEST lacks the translocation characteristic of cellular congenital mesoblastic nephroma, and most reported cases are benign tumors (1,2,7,8) .The presenting symptoms are flank pain, hematuria, or symptoms of the urinary tract.The lesion corresponds to an incidental finding in 25% of the patients (1,2,(7)(8)(9) .On gross examination, MEST is a centrally located, circumscribed, solid-cystic kidney lesion that frequently extends into the renal pelvis.A partial or complete capsule is often present.The tumor infrequently shows an infiltrative border.Mean tumor size reported in the literature was 6 cm (1,2,(8)(9)(10)(11)(12)(13)(14) .
Spindle cells show positive immunoexpression for actins, desmin, vimentin, smooth muscle actin, and estrogen and progesterone receptors.The epithelial component exhibits positive immunoexpression for cytokeratins and often vimentin.Positivity for estrogen receptor has been described in the epithelial element, and it has also been noted in male patients who have received antiandrogenic therapy for prostate cancer.MEST has been considered a cystic nephroma that has acquired cellular, ovarian-like stroma secondary to hormonal influences (1,3,14,19,23,27,28) .In the present report, authors described immunopositivity for estrogen receptor in the stromal component of a male patient who developed a MEST of the kidney.Some authors consider this unexpected finding associated with tumor loss differentiation and the activation of estrogen-related protein p29, which is a possible factor of influence on some gender-specific estrogen-associated tumors (4,6,8,9,14,18,23) .
The histogenesis of MEST is unknown.Hormonal imbalance during the perimenopausal period can be related to the activation of a misplaced immature or fetal mesenchyme, which harbors the capacity for a dual, epithelial and mesenchymal differentiation.Some authors suggest the hypothesis of müllerian remnants developing neoplastic transformation due to excessive hormonal stimulation (1,2,6,8,11,18,23,27) .
The differential diagnosis includes adult nephroblastoma, cystic nephroma, and sarcomatoid renal cell carcinoma.The lack of cellular anaplasia rules out these tumors.The absence of blastema excludes nephroblastoma, and cystic nephroma typically shows a thin and fibrous stroma.MEST have been treated with surgical excision, and a few cases of recurrence, malignant transformation, and metastases development have been reported (6,8,9,11,13,15,16,23,24,27) .

figuRE 1 −
figuRE 1 − Mixed epithelial and stromal tumor of the kidney: a circumscribed, light brown, solid tumor, with cystic areas figuRE 3 − Mixed epithelial and stromal tumor A) a biphasic tumor composed by spindle cells and epithelial elements; B) positive immunoexpression for estrogen receptor in the stromal component, streptavidin-biotin, 400×; C) positive control for estrogen receptors in breast invasive ductal carcinoma, streptavidinbiotin, 200×; D) epithelial covering cystic formations, hematoxylin-eosin, 40×.

taBLE -
Summary of published cases of MEST of the kidney