Metanephric stromal tumor: An unusual pediatric renal neoplasm.

A renal tumor in a 14-month- old child, who was initially diagnosed as mesoblastic nephroma, but on review post surgery was diagnosed as hyper-differentiated metanephric stromal tumor, with its excellent prognostic outcome. An attempt is made to document imaging features that may enable one to suspect this rare condition. The literature is reviewed with emphasis on its distinction from its look-alikes in the pediatric age group.

INTRODUCTION

Incidence of pediatric renal neoplasia is 100 per million, out of which almost 90-95% are Wilms’ tumors. Metanephric tumors are related to Wilms’ tumors minus their aggressiveness. Closest of these metanephric tumors to Wilms’ are the epithelial stromal tumors. Metanephric stromal tumors are hyper-differentiated with no metastasis reported. Recurrence has been reported only in one case which was managed without any further treatment and is still surviving years later.[1] The 5 year survival of these rare metanephric tumors following nephrectomy is almost 100% even without adjuvant chemotherapy.

CASE REPORT

A 14-month-old was referred for CT scan for evaluation of a right renal mass diagnosed following a sonographic scan done for right flank pain. The patient had no history of hematuria or fever. The sonographic diagnosis was Wilms’ tumor. CECT scan [Figure 1] revealed a large non-enhancing, well-defined predominantly cystic renal mass occupying superior pole of right kidney with evidence of osseous tissue mass eccentrically located. There was no evidence of ureteric or bladder extension. The vascular pedicle was uninvolved. The patient underwent right nephrectomy. A pathological diagnosis of CMN was given. Subsequent review of histopathology along with IHC results confirmed the diagnosis as metanephric stromal tumor (MST) of kidney.

Figure 1

Coronal CECT shows a large non-enhancing, well-defined predominantly cystic renal mass occupying superior pole of right kidney with evidence of eccentrically located osseous tissue

Gross pathology: Right nephrectomy specimen has a large cystic mass in its superior part. On cut section, the contents are altered hemorrhagic fluid with tan colored wall that has a solid eccentrically located osseous tissue mass where cyst abuts normal renal tissue [Figure 2].

Figure 2

Cut section of right nephrectomy specimen showing large cystic cavity in its superior half, with a solid eccentrically located osseous tissue mass

Microscopy: Sections showed structure of a tumor composed of bland spindle cells arranged in fascicles and sheets [Figure 3]. The spindle stromal cells showed round to oval vesicular nuclei with minimal nuclear pleomorphism. Mitotic figures were not seen. The spindle cells were wrapped around immature renal tubules in an onion skin fashion. The lining of the renal tubules was composed of tall columnar cells showing pseudo-stratification. Blood vessels entrapped among the stromal cells showed medial hypertrophy. However, features of angiodyplasia were not noted nor did the glomeruli present at the edge of the tumor show juxta glomerular hyperplasia. Those stromal cells arranged around the tubules in an onion skin fashion showed positivity for CD 34 [Figure 4] demonstrating the immature nature of these cells. The spindle cells in the surrounding areas showed focal positivity for smooth muscle antigen (SMA). The renal tubules showed positivity for cytokeratin (CK). In sections taken from the edge of the tumor, heterologous elements like mature bone and adipose tissue were present.

Figure 3

Low power view showing entrapped immature renal tubules amongst proliferating spindle cells [×100× Periodic Acid Schiff’s (PAS) stain]

Figure 4

Spindle cells around the renal tubules showing positivity for CD 34 [×200×]

No chemotherapy was given to the patient.

DISCUSSION

It was not until end of last millennium that a separate entity of MST came to be recognized with its attendant benign nature and consequent very favorable outcome. Till that time, these tumors were labeled as mesoblastic nephroma tumors. MST is a hyper-differentiated tumor arising from stromal cells.

In the year 2004, WHO sub-grouped renal stromal tumors under a separate subhead based on cell of origin.[2] In one large series of 31 patients of MST from National Wilms’ tumor Study Pathology Centre (NWTSPC), Argani reviewed, analyzed, and recorded pathological findings of this condition.[3] Metanephric adenoma (MA) (more aggressive) and metanephric stromal tumor MST (less aggressive) are at ends of spectrum wherein metanehric adenofibroma (MAF) lies in middle of these stromal tumors.[4] Kadar et al reported a case of MST in a child presenting as cystic mass with radio logically undetected small solid component because of blurring infiltrative margins.[5] Four of 31 reported MSTs in Armani series also large cystic component as in our case.

Although grouped together they occur at different ages. While MA occurs mostly in females in 5th and 6th decade, MAF occurs in late childhood and early adult age, and MST occurs in early infancy/childhood (median age 13 months and peak at 2 yrs).[3] No bilateralism was noted. In fact MST is known to occur in early childhood along side with CMN, clear cell sarcoma of kidney (CCSK), rhomboid tumor of kidney (RTK), renal ossifying tumor of infancy (ROTI), and Wilms’ tumor. These constitute the differential of a renal mass in a young child. The stromal component of MST is distinctive from CMN and other renal tumors. It is important to correctly recognize MST which has by far the most favorable outcome as compared to others such as cellular variety of CMN, CCSK, RKT, and atypical Wilms’ tumors, which are far more aggressive and have stormy course needing adjuvant chemotherapy in addition to surgical nephrectomy.

These tumors were labeled CMNs prior to their recognition as distinctive MST by Argani et al. It is often difficult to distinguish it from CMN, as both are cantered around renal medulla and depict bland spindle cells. However, the presence of scalloped subtly infiltrative margins contrasts with invasive character of CMN. In addition, low power nodularity, the presence of peritubular or perivascular onion skinning/ collarette indicate MST. Heterologous tissue presence and positivity with CD34 and negativity for desmin are diagnostic of MST. Another mimic is CCSK which can be distinguished by vascular pattern consisting of regular branching. CCSK has negative immunoreactivity for CD34 and s-100 proteins.

Distinction from MAF is difficult at times and is on the other side of the continuous spectrum which features in addition a bland embryonic epithelial component (hence biphasic). MSTs have been found to morphologically resemble intralobar nephrogenic rests (ILNR) which are precursors of Wilms’ tumor ILNR have characteristic blastema or fat, which is lacking in MST. It has been postulated that MST is mature form of ILNR wherein blastema cells have disappeared over a period. Their close relationship is evident from heterologous differentiation in both Wilms’ and MST. Further, Argagni has reported multiple cases of Wilms’ tumor that arose in association with lesions that were morphologically identical to MST.

MSTs present as abdominal mass or as incidental finding. The outlook following surgical nephrectomy is excellent with no reported recurrence /metastasis. In contrast, atypical Wilms’ and CCSK metastasize widely while even RRT and cellular CMN occasionally metastasize.

The confirmation of the diagnosis is based on histopathological features and immunohistochemistry (CD34 and Vimentin).

No attempt has been made to clearly document imaging characteristics of MST yet. In a young child having a non-enhancing unencapsulated unilateral renal tumor mass lesion having large central cystic component (seen in some of patients of MST) with evidence of heterologous elements such as cartilage, glial tissue, or bone on CT, a possible MST diagnosis must be considered. Post nephrectomy, the specimen must be examined for CD34 positivity which will help it distinguish from CCSK. If the diagnosis of MST is confirmed, adjuvant chemotherapy with its enfeebling side effects may be avoided altogether.

The incidence of MST is so miniscule that many clinicians / radiologists / pathologists may not come across even a single case in their lifetime, but their importance lies in their extremely benign nature, so clinician must be aware of its existence and must be considered in differential of early childhood renal masses.