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.
