In this paper we present three cases of TWT and correlate our findings with a brief review of literature.
Case 2: A 20-month-old male presented with a large abdominal mass. CT scan revealed a well-defined, 10 cm, partly cystic mass arising in the lower pole of the right kidney and compressing the renal pelvis causing hydronephrosis (Figure 3A). The contralateral kidney appeared normal. The nephrectomy specimen measured 11 x 8.5 x 7 cm and weighed 422 g. The cut section revealed a well circumscribed greyish white 10 cm mass involving the kidney. Part of the mass projected into the renal pelvis in a coarse nodular and papillary pattern (Figure 3B). A 2.4 cm rim of unremarkable renal tissue was noted at the periphery of the mass. On microscopic examination the tumor revealed foci with a triphasic pattern consisting of blastemal, epithelial and mesenchymal components. The tumor projecting into the renal pelvis had a predominant triphasic pattern (Figure 3C). Approximately 90% of the tumor showed rhabdomyomatous elements with occasional foci of smooth muscle differentiation (Figure 3D-E).
The tumor was limited to the kidney. Surgical resection margins and hilar lymph nodes were free of tumor. There was no anaplasia. The tumor cells were immunoreactive for WT1 antibody. Molecular studies for WT1 mutation by sequencing revealed wild-type WT1 gene. No mutation was detected (Figure 2).
Case 3: An 11-year-old female presented with an abdominal mass discovered following trauma. CT scan showed an 18.0 cm right renal mass extending from the lower part of the kidney (Figure 4A). The mass compressed the inferior vena cava and renal pelvis causing hydronephrosis. The left kidney, liver, pancreas and bowel loops appeared essentially unremarkable. The nephrectomy specimen measured 22 x 15 x 10 cm and weighed 1242 g. The cut surface revealed a gray white to dark tan mass in the kidney measuring 18 x 13 x 6 cm with extensive necrosis and hemorrhage. Multiple cystic spaces were present in the upper pole. A thin rim of normal renal parenchyma was noted at the periphery in the lower pole (Figure 4B). Histologically most of the tumor consisted of smooth muscle elements and extensive mature epithelial glandular elements with squamous and goblet cell differentiation (Figure 4C-G). Scattered islands of the usual embryonal epithelial, stromal and blastemal elements were identified. There was no anaplasia. No capsular or lymphovascular invasion was noted. One hilar and one paraaortic lymph node revealed foci of metastatic tumor. Immunohistochemical staining for WT1 was positive. Molecular studies for WT1 mutation by gene sequencing revealed wild-type WT1 gene. No mutation was detected (Figure 2).
A review of the literature indicates that till date 30 cases of TWT have been documented (Table I)[4-28]. Among the reported cases the age ranged from 3 month to 7 years, which is similar to that seen in the classic WT[1-3]. In addition, one case of TWT in an adult patient has been recorded[19].
Table I: Reported cases of Teratoid Wilms Tumor (TWT) in literature
Extra renal WTs account for around 3% of WTs. Approximately 100 well-documented cases have been reported. These tumors have been encountered in a variety of locations including the retro peritoneum, inguinal and para testicular region, female genital tract, bladder, thorax, and lumbosacral region[2]. A review of the literature revealed only five reported cases of extra renal TWT[29-32]. The locations of tumors in these reports are sacrococcygeal region, pelvicalyceal junction, vagina and abdomen (Table II).
Table II: Reported cases of extra renal Teratoid Wilms Tumor (TWT)
The reported cases of TWT may be divided into three morphologic categories depending upon the predominant histologic pattern. Some tumors may contain a predominant mesenchymal component such as smooth muscle or rhabdomyomatous elements. These tumors may be categorized as mesenchymal predominant. Some of these tumors have a predominance of well-differentiated rhabdomyomatous component. Such tumors have also been called fetal rhabdomyomatous nephroblastoma[33]. However, since these tumors seem to fall within the definition of TWT, a separate designation is perhaps unnecessary. The second category includes tumors in which heterologous epithelial components are predominant. Most of these seem to contain abundant squamous epithelium and have been called epithelial or squamous predominant. A third type of TWT may be composed of a heterogeneous mixture of heterologous epithelial and mesenchymal elements without any of these components becoming predominant. This type of TWT may be categorized as having a mixed pattern.
The most important differential diagnosis for TWT is intra renal teratoma and metastasis from a germ cell tumor arising in another location. Teratoma of the kidney is extremely rare and most have been dismissed as cases of TWT or retroperitoneal teratomas secondarily invading the kidney. The differentiation between these two neoplasms in the kidney is often problematic. Although teratomas and teratoid WT may have similar histology, teratomas display unequivocal organogenesis such as stratified squamous epithelium associated with skin adnexa, intestinal mucosal epithelium surrounded by smooth muscle bundles, and neuroglial tissue associated with choroid plexus epithelium[34]. In occasional cases of TWT, the serum AFP levels may be elevated. This finding should not be interpreted as an argument in favor of a renal teratoma[10,18,30]. In cases where adipose or smooth muscle elements are predominant, the possibility of angiomyolipoma may also be considered in the differential diagnosis. Angiomyolipoma is composed of mature smooth muscle and adipose tissue. Angiomyolipoma belongs to the perivascular epithelioid cell family of tumors, known to be immunoreactive for smooth muscle and melanocytic markers[35]. Furthermore these tumors lack the embryonic cellular elements of blastemal tissue that are usually present in TWT.
Wilms tumors may manifest genetic abnormalities in one of the two regions in the short arm of chromosome 11 namely 11p13 (WT1) and 11p15 (WT2). Cytogenetic studies in nine reported cases of TWT have revealed 11p deletion or monosomy 11[2]. The WT1 gene is located on the short arm of chromosome 11 (11p13). It spans approximately 50 kb and includes 10 exons, encoding a 3 kb mRNA. The carboxyl-terminal portion (Exon 7-10) contains 4 zinc finger motifs, which form the DNA-binding domain. WT1 can bind, through its zinc fingers, to the promoter regions of a multitude of putative downstream target genes. All mutations in WT1 alter the structure of the DNA binding domain, which changes its ability to bind to DNA, resulting in loss of function[2].
Park et al. described the CT features of teratoid Wilms: It usually appears as a cystic renal mass with multifocal, solid components containing fatty elements and occasional calcifications. These authors also noted that theses tumors have diverse features, such as bilaterality, a tendency to extend into the collecting system, and association with nephroblastomatosis[36].
Our series of three cases although small equals two other largest series reported till date. The salient features of all the reported cases, including the current series, is briefly presented in Table I. Our cases were relatively younger than most of the reported series. The histological features in our series were more or less comparable to other reported cases; however, all our cases had good outcome, despite one of the cases showing lymph node disease (Case 3). Although germline mutations of WT1 gene have been detected in children with genetic predisposition to WT mutational analysis of our cases was limited to tumor tissue only. Similar to the reported incidence (~20%) of WT1 mutations in sporadic WT only one of our three cases showed WT1 mutation[2]. Interestingly, data on WT1 gene mutation in TWT is sparse and our study indicates that they are not dissimilar to typical cases of WT with mutation being present in only a small minority.
The treatment of TWT patients has not yet been established because of the entity's rarity and varying tumor components. Surgical resection appears to be the treatment of choice due to relatively inconsistent tumor response to chemotherapy and radiation. Most of the reported cases have been shown to be free of recurrence or metastatic disease following nephrectomy. In two cases, however, pulmonary metastases were reported (Table I). One of our patients also had metastatic tumor to the regional lymph nodes. TWT cases do not usually respond to chemotherapy. Resistance to chemotherapy may be due to the presence of a high proportion of relatively mature heterologous tissues within the tumor. As the neoplastic tissues continue to differentiate, tumors may even increase in size while undergoing therapy, giving the false impression of an aggressive biology.
CONFLICT OF INTEREST
None of the authors involved in this work has any conflicts
of interest, financial or otherwise.
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