Exophytic benign mixed epithelial stromal tumour of the kidney: case report of a rare tumour entity

The mixed epithelial and stromal tumour (MEST) of the kidney represents a recently described benign tumour, which has to be distinguished from other renal neoplasms. The term MEST was first introduced by Michal and Syucek in 1998[1]. Morphologically, the tumour is characterized by a biphasic proliferation of stromal cells with an epithelial component showing cystic dilatation. The vast majority of cases show a benign course without tumour recurrence [2–4].

We report the unusual case of a MEST arising from the left kidney as a cystic tumour in an exophytic fashion. Since the diagnosis was secured by intraoperative frozen section, tumour excision without nephrectomy could be performed as treatment of choice.

Mixed epithelial and stromal tumour (MEST) represents a recently described tumour entity of the kidney of unknown etiology [2, 5, 6]. In the past other synonyms, such as cystic harmatoma of the renal pelvis, adult mesoblastic nephroma, and cystic nephroma with "cellular" or "ovarian-type" stroma were applied [2]. About 50 cases have been reported in the literature so far [2, 3, 5, 7, 8]. Typically, the tumour presents in perimenopausal woman as a combined solid and cystic tumour mass. The mean age of clinical presentation is about 45 years.

The patients usually present to the urologist with non-specific symptoms, such as flank pain, hematuria, or symptoms primarily suggestive of genitourinary infections. The mean tumour size at primary diagnosis is about 6 cm in diameter [2, 5, 6]. Different hypothesis have been proposed for its origin. The most popular postulation is based on a disturbed hormonal environment, which is typically observed in perimenopausal women or which may be caused by therapeutically applied female hormones. Thus, hormonal imbalance might induce the proliferation of a misplaced immature or fetal mesenchyme, which harbours the capacity for a dual, epithelial and mesenchymal differentiation [2, 5, 6]. This theory is driven by the observation of the expression for the estrogen and progesterone receptor within the stromal cells by nearly all cases of MEST [2, 5, 6]. In addition, the latter hypothesis is supported by a study showing that most of the affected women had a long history of treatment with estrogens. However, the only male patient reported so far had a history of diethylstilbestrol therapy for 7 years, applied because of treatment for prostatic cancer.

Nearly all cases described so far demonstrated a benign course without tumour recurrence. However, four cases of aggressive MEST have been described in the literature so far [9–12]. Three patients with MEST with local recurrence of tumour showing a fatal course have been described. In two patients, the recurrent tumour was composed exclusively of malignant transformed stroma [10]. One case displayed malignant transformation of MEST to a sarcomatoid carcinoma with heterologeous differentiation [9].

The differential diagnoses include renal tumours, which can show at least a partly cystic morphology, such as partially cystic differentiated nephroblastoma, multilocular cystic renal carcinoma, angiomyolipoma with epithelial cysts or in rare cases synovial sarcoma [2, 5, 6].

MEST demonstrate morphological overlap to cystic nephroma, with which it can be confused [13, 14]. Both entities show some remarkable similarities including sex predilection, age distribution, and morphological attributes of the epithelial and stromal components as well as immunohistochemical profile [15]. Albeit there are some variations in the individual categories with a higher prevalence of stromal-to-epithelial ratio, prominent ovarian stroma, smaller cysts more common in MEST; in contrast larger cysts with only thin septa (with septa being smaller than 5 mm) and in addition a lower stromal-to-epithelial ratio are typically observed in cystic nephroma [2]. However, the presence of ovarian-like stroma and müllerian-related immunohistochemical markers raise the possibility that these tumours might originate from müllerian remnants displaced during embryogenesis [2, 5, 16].

Since some tumours have gross and microscopic features intermediate between cystic nephroma and MEST, it is considered that both tumours might represent different morphological variants of the same tumour entity [2, 5–7, 14, 17, 18]. Therefore, Turbiner et al. (2007) proposed to summarize both tumours under the unifying term "renal epithelial and stromal tumour" (REST)[2]. However, this proposal is primarily based on the observation of an ovarian-like stroma in both tumour entities, but since this kind of stroma is also observed in obstructed kidneys, even without neoplasia some authors consider the stromal differentiation as a form of reactive metaplasia [17, 19]. In a recent study, Zhou et al. [20] investigated the relationship of cystic nephroma and MEST compared to other renal tumours and normal kidney by using mRNA based gene expression profiling and additional extensive histologic analyses. Unsupervised clustering of mRNA expression profiles demonstrated that cystic nephroma and MEST had very similar expression profiles, which were distinct from other renal neoplasms. Thus, the data of Zhou et al. provide additional convincing molecular evidence that cystic nephroma and MEST represent indeed one disease entity. However, since there are no specific molecular markers for the differentiation of MEST from cystic nephroma and there are no further clues to the origin of both tumour entities, a definitive classification remains outstanding [17].

Mixed epithelial and stromal tumour represents a distinctive benign tumour of the kidney that should be distinguished from other cystic renal neoplasms. Prognosis of this tumour is favourable in nearly all cases published so far. Only rare cases of malignant transformation have been published. In summary, MEST represents a benign mostly cystic tumour of the kidney, which is predominately observed in middle aged, perimenopausal women. Knowledge of this certain but rare tumour entity is important, since in most cases conservative surgery with preservation of kidney function is the therapy of choice.

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.