Keywords
extrarenal Wilms tumor - retroperitoneum - nonanaplastic - childhood malignancy - intermediate risk
Introduction
Wilms tumor (WT), also known as nephroblastoma, is the frequently encountered abdominal solid tumors in children. In fact, it nearly entirely originates from the kidneys and accounts to 95% of renal tumors in children.[1] In rare cases it may develop outside of the kidney termed as extrarenal WT (ERWT) when both kidneys are normal and the tumor should morphologically resemble to primary intrarenal WT.[2]
[3] ERWT was first described by Moyson et al in 1961 and accounts for 0.5 to 1% of WT diagnoses.[4] Primarily, ERWT arises in the inguinal region and the retroperitoneum. It can also originate from the mediastinum, adrenals, colon, spinal cord with paravertebral soft tissues, pelvis, urinary bladder, uterus, cervix, ovary, prostate, testis, scrotum, and lumbosacral regions.[5] The most validated hypothesis states that ERWT can develop along the craniocaudal migration of the primitive mesonephros and metanephros cells.[6]
Case Report
A 4-year-old girl was referred for further management, postexcision of an abdominal mass. She complained of pain abdomen, and an abdominal mass in the left lumbar region was noticed by her grandmother for the past 1 month. Complete blood count showed anemia with hemoglobin of 10.4 g%, while the other parameters were normal. Her renal function test was within normal limit. Contrast-enhanced computed tomography scan of the abdomen revealed a well-circumscribed smooth marginated, solid mass with significant perilesional vascularity measuring 6 × 5.5 × 5.2 cm, in the retroperitoneum, extending from the L4-S1 vertebrae, at the level of bifurcation of aorta ([Fig. 1]). All the abdominal and pelvic organs including bilateral kidneys and ovaries were normal. The histopathology slides were reviewed showing an encapsulated malignant neoplasm composed of triphasic components with predominance of blastemal and epithelial elements. Small monomorphic round to ovoid blastemal cells were arranged in lobules separated by fibrous septae. The epithelial components showed vague rosetting and papillary pattern with presence of glomeruloid and tubular structures. Focal stromal component having bland spindled cells is noted. Features of anaplasia were absent. Large areas of necrosis, with high mitosis (4–5/10 high-power field), and vascular emboli were noted. Preliminary morphological diagnosis of malignant small round tumor was made ([Figs. 2] and [3]). Further immunohistochemistry study showed positivity to CD99, PAX8, WT1, TLE1, Bcl2, and desmin, and negativity to EMA, CK7, synaptophysin, NKX2.2, and SALL4. cytokeratin (CK) highlighted the tubules and p53 expression is wild-type ([Figs. 4] and [5]). The final diagnosis of ERWT, nonanaplastic, mixed type, intermediate risk was made. Based on operative records of intraoperative spillage, stage III was assigned.
Fig. 1 Contrast-enhanced computed tomography (CECT) abdomen: a large well-circumscribed smooth marginated solid extrarenal mass with significant perilesional vascularity in the retroperitoneum.
Fig. 2 Photomicrograph showing triphasic blastemal, epithelial, and stromal components (hematoxylin and eosin [H&E], 200×).
Fig. 3 Photomicrograph shows abortive glomerulus with epithelial cells in tubular and papillary pattern (hematoxylin and eosin [H&E], 200×).
Fig. 4 The tumor cells show strong nuclear positivity to PAX8 and WT1 (immunohistochemistry [IHC], 200×).
Fig. 5 The tumor cells showing strong cytoplasmic staining to desmin. CK highlights the tubules (immunohistochemistry [IHC], 200×).
Discussion
WT is among the most prevalent renal neoplasm, accounting for 7 to 8% of all pediatric tumors in children under the age of 15, with a slight female predominance.[1] The clinical and age presentations of both renal WT and ERWT are identical, ranging from 12 to 48 months (average 36 months). The most accepted theory is the Connheim's theory, emphasizing the persistence of embryonal cells, which can undergo malignant transformation subsequently along the line of embryogenesis.[7] One of the two regions on chromosome 11 short arm, 11p13 (WT1) or 11p15 (WT2), may exhibit genetic abnormalities.[8] Both renal WT and ERWT follow the same histological risk classifications as per the Children's Oncology Group, which has two subtypes of nonanaplastic nephroblastoma (favorable histology) and anaplastic (focal and diffuse) nephroblastoma (unfavorable histology); the International Society of Pediatric Oncology (SIOP) classification distinguishes the following types of nephroblastoma: completely necrotic, epithelial, stromal, mixed, regressive, focal anaplasia, diffuse anaplasia, and blastemal.[9] Coppes et al analyzed 34 ERWT cases and noted that stage I accounted for 30%, II for 10%, III for 57%, and IV for 3% of all cases.[3] According to Shojaeian et al, favorable histology was noted in most of the 87 reported cases of ERWT.[5] Karim et al found that 70% of ERWTs were in stage II and 23% in stage III, while distant metastasis was reported in 6% . The majority of the ERWTs have favorable histology; however, in 11% of instances, local recurrence has been reported, which is similar to the 15% predicted recurrence rate in classic renal WT with favorable histology.[6] Similar to these studies, our case had mixed type, nonanaplastic (favorable histology) of intermediate risk category and belonged to stage III. While a thorough systemic search for the tumor dissemination is necessary, ERWTs seldom metastasize, lungs and liver being the most prevalent sites. Metastasis was observed in 3% of the reported cases.[5] It is important to keep in mind that, in addition to retroperitoneal ERWT, other embryonal tumors, such as mixed Mullerian tumors, hepatoblastoma, Burkitt's lymphoma, and embryonal rhabdomyosarcoma, can occur.[7] Surgical excision is the crucial mainstay in the management of ERWT; however, since there also reports of increased incidence of tumor rupture in these cases due to deep seated retroperitoneal presentation, a diagnosis on a small biopsy may circumvent the need of a complicated upfront surgery.[10] These are now managed using the same strategy as is recommended for conventional WT. The pediatric oncologist planned to treat with vincristine and actinomycin D for 28 weeks plus 15 Gy radiation as per SIOP. Patient is undergoing chemotherapy/radiotherapy and will be kept under close follow-up.
Conclusion
ERWT is a rare childhood malignancy. Owing to exceptional rarity of this tumor with inadequate data in the literature, it still represents a diagnostic problem. Upcoming novel molecular biological markers will probably become even more important in the future for both differential diagnosis and prognosis of tumors. Thus, the current gold standard for diagnosis, subtyping, and prognosis is meticulous histopathological evaluation combined with extensive immunohistochemistry analysis. It highlights the significance of prompt histopathologic diagnosis and clinical awareness when confronting unusual masses in the abdomino-pelvic regions. The suggested treatment strategy for ERWT is comparable to that of conventional renal WT.
