Mixed epithelial and stromal tumor (MEST) is a biphasic adult renal lesion composed of solid and cystic areas containing spindle cell stroma and epithelium that lines the tubules and cystic spaces. While most MEST lesions are benign, rare cases with malignant morphology and biology have been reported. We present a case of mixed epithelial and stromal tumor of the kidney (MEST) with extension into the inferior vena cava in a young adult male. We discuss the differential diagnosis of MEST in the context of other biphasic cystic renal lesions and the significance of vascular involvement in the setting of an otherwise benign tumor morphology.
Mixed epithelial and stromal tumor (MEST) is a biphasic adult renal lesion containing solid and cystic areas composed of spindle cell stroma and epithelium that lines the tubules and cystic spaces [
A 27-year-old male presented with a 1-day history of intermittent gross painless hematuria. His past medical history included herniated lumbosacral disk with radiculopathy, otherwise unremarkable. Social history included current smoking, 6 pack/year, and occasional EtOH. The patient was single and had no children; family history was negative for genitourinary malignancies. Physical examination was unremarkable with BMI 23 and BP 120/86 and no prescribed medicines or drug use. Laboratory tests showed normal CBC, normal coagulation profile, and normal renal function.
Axial, contrast-enhanced CT demonstrated a centrally located, 4 x 4 x 4.6 cm, lobulated mass invading the renal vein and extending into the lumen of the infrahepatic inferior vena cava (Figure
Axial, contrast-enhanced CT demonstrates a centrally located lobulated mass invading the renal vein and extending into the lumen of the inferior vena cava.
Right radical nephrectomy, partial adrenalectomy, inferior vena cava tumor thrombectomy (infrahepatic), and extended retroperitoneal lymphadenectomy were performed; flexible cystoscopy performed during this surgery showed a bulbar urethral stricture (not clinically significant) and otherwise normal bladder. The intravascular tumor pedicle was easily removed intact from the vein lumen by pulling.
Gross examination of the nephrectomy specimen demonstrated a centrally located tumor with no gross invasion of adjacent tissue but with the pedicle extending into the inferior vena cava (Figure
Gross image of the intrarenal mass and an elongated pedicle extending into the lumen of the inferior vena cava. The mass is lobulated and partially cystic and the pedicle has a smooth border.
Microscopically, the tumor was well demarcated with an elongated pedicle bulging into the renal pelvis and renal vein and a biphasic morphology with spindle cell stroma and a benign epithelial monolayer lining the cystic spaces (Figure
Cystic and biphasic tumor with benign, spindle cell stroma, focally resembling ovarian stroma, arranged with increased density in pericystic areas. Epithelial lining of cystic spaces is composed of a monolayer with cuboidal, flattened, and, focally, a hobnail appearance. No morphologic features of dysplasia are identified. Hematoxylin and eosin original magnification: 300x.
The stromal cells were diffusely and uniformly positive for SMA (Figure
The spindle cell stroma diffusely positive for smooth muscle actin. Immunoperoxidase stain for smooth muscle actin; original magnification: 125x.
Epithelium lining of cystic spaces showing diffuse and strong positivity for CK7. Immnuoperoxidase stain for CK7; original magnification: 200x.
The tumor pedicle extending into the inferior vena cava showed similar morphology except for some edema and a focal procedure-related hemorrhage. Specifically, no epithelioid morphology and no tumor necrosis or mitoses were seen despite extensive sampling. The pedicle appeared to be floating in the vascular lumen without attachment to, or invasion of, the vascular wall (Figure
Tumor within the renal vein lumen with tumor pedicle seen on the right and vessel wall on the left. Hematoxylin and eosin original magnification: 300x.
FISH studies for
A diagnosis of “mixed epithelial and stromal tumor (MEST) of the kidney with extension into IVC” was rendered. After surgery, the patient recovered uneventfully and no recurrences have been reported at 3 years’ follow-up.
MEST is a rare, adult, biphasic tumor of the kidney [
MEST tumors are well circumscribed, range widely in size (from 2 cm to 24 cm), and typically show no gross invasion of adjacent tissue, which was also the case in the tumor described in this report. Typically for MEST, the current tumor was centrally located, with involvement of the renal pelvis, and displayed a cystic architecture with grossly apparent stromal nodules [
As seen in MEST tumors, the stroma in the current tumor was also positive for smooth muscle markers (SMA and desmin), while the ovarian-like areas were positive for CD10 and melanocytic markers (HMB-45 and MART1 ) were negative [
Clinically, most MEST tumors have been reported in perimenopausal women (mean age of 52 years) but rare male patients and exceptionally rare cases of older children have also been reported [
While most MEST are benign, rare malignant tumors (17 cases thus far) have been reported [
Angiomyolipoma with epithelial cysts (AMLEC) is a smooth-muscle-predominant (or “fat-poor”) angiomyolipoma, which also contains epithelial cysts and displays mixed, solid, and cystic architecture [
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Congenital mesoblastic nephroma (CMN), the most common congenital renal neoplasm, also shows a biphasic architecture with cysts and tubules embedded in abundant spindle cell stroma and, hence, is morphologically very similar to MEST. In fact, earlier literature reports of “adult mesoblastic nephroma tumors” most probably represent MEST. Thus, currently, according to the 2016 WHO classification of renal tumors, the distinction between these two entities is based on the patient’s age, with CMN being considered a distinctly pediatric tumor [
CMN of the cellular type has a specific chromosomal translocation, which leads to fusion of the
Among MEST malignancies, 14 out of 17 reported tumors showed stromal malignancy with features of undifferentiated sarcoma, which were synovial sarcoma-like or, on rare occasions, possessed rhabdomyosarcoma-like and chondrosarcoma-like features [
Malignant MEST with a sarcomatous stromal component shows morphologic overlap with primary renal synovial sarcoma (RSS) (formerly “embryonal sarcoma of the kidney”) [
Thus far, a diagnosis of MEST appears to be based on the exclusion of other tumors with overlapping morphologies, both benign and malignant. Also, no MEST-specific molecular signatures have been detected and, among the discriminating factors in the differential diagnosis, the patient’s age appears to play a seemingly decisive role [
Among the poor prognostic factors in renal tumors, advanced stage, margin status, and renal sinus/vascular involvement are routinely considered. The current case showed a morphologically benign MEST with tumor extension into the IVC. However, in view of the apparently benign tumor morphology, we interpreted intravascular extension as an unusual tumor growth pattern rather than an indication of malignancy.
The intravascular component of the tumor showed no features of malignancy: no epithelioid features in the smooth muscle stroma, no necrosis, and no features of sarcoma; the only notable feature of the tumor was hemorrhage, both old and recent. Two other cases of morphologically benign MEST with renal vein involvement were also recently reported and both were apparently also clinically benign [
A similar situation, with a seemingly benign tumor involving the renal vein, has been reported in rare cases of renal oncocytoma. Renal oncocytomas with intravascular extension into the renal vein [
A case of MEST with inferior vena cava involvement lacking cytologic features of malignancy appeared to be a benign tumor. However, caution is advised in the management of MEST, since incomplete tumor resection can lead to recurrence and, in rare cases, malignant transformation can occur with a grim prognosis. Hence, a careful long-term follow-up is warranted. Moreover, caution is advised in the management of patients based on limited tumor sampling, such as core biopsy or cytology.
The authors declare that they have no conflicts of interest.