ABSTRACT
Ewing’s sarcoma of the kidney
is a rare malignancy, especially in the pediatric population. It belongs to
what is called the Ewing sarcoma family tumors. It is not common as a
differential diagnosis in renal tumors during childhood, with a nonspecific presentation
as abdominal pain and hematuria. It is usually seen in late childhood and
adolescent patients. The radiological features are neither specific nor
pathognomonic. So, we rely on histopathology, immunohistochemistry and
molecular/ cytogenetic studies for diagnosis.
Once the diagnosis is
established, multimodal chemotherapy is started according to the treatment
protocols found in the literature and centers’ experiences in these cases.
Reporting and publishing these rare tumors
will help in understanding the course of the disease and its response to the
treatment protocol.
Key Words: Ewing’s sarcoma of the
kidney.
RMS April 2022; 29(1): 10.12816/0060315
Introduction
Ewing sarcoma of the kidney is
a rare renal tumor in children with 10 cases reported in the literature since
its first description in 1975(1).
It is mainly a genetic disease, with some sporadic cases. Most tumors
contain a translocation mutation with a fusion between the EWS gene on
Chromosome 22 and FLI1 on Chromosome 11 t (11,22). The original cell of this
tumor is unknown; but, the thought till now is that it is derived from neural
cells and neural crest cells (2).
We report a case of a 10 year
old male patient diagnosed with Ewing sarcoma of the kidney. After radical
nephrectomy, a significant response to multi-agent chemotherapy and
radiotherapy was observed, with an excellent outcome.
Case
presentation
A 10 year old male, otherwise
healthy, presented to the emergency room with a history of sudden onset of
gross hematuria associated with right flank pain. There was no history of
weight loss, decreased appetite, night sweats, vomiting, or dysuria. No
dysmorphism or neurological manifestations were seen.
Blood tests were normal, urine analysis
revealed bloody sample, urine culture was normal.
A CT scan of the abdomen
showed a well- defined mixed density soft tissue mass lesion measuring 78x62 mm
arising from the upper pole of the right kidney, possible lymph nodes in the
right aortocaval region of the upper abdomen (Figure 1a and 1b). Chest CT
(Figure 3) revealed no evidence of lung nodules. So, the patient underwent right-sided radical
nephrectomy on 17/7/2018 as shown in the postoperative CT scan (Figure 2).
Histopathology revealed a
malignant small round blue cell
tumor.
Immunohistochemical (IHC)
stains revealed positive staining of the tumor cells for CD99, vimentin and
neuron specific enolase (NSE) (Figure 4). The differential diagnosis was
blastema predominant Wilms tumor versus Ewing sarcoma /PNET. The paraffin
blocks containing tumor tissue were referred to another center for FLI-1 IHC
stain and Fluorescence in situ hybridization (FISH) studies. The results were
positive for FLI-1 IHC stain and EWSR1 gene rearrangement by FISH confirming
the diagnosis of Ewing sarcoma ,This technique was performed using vysis LS1
EWSR1 dual color, break -apart rearrangement probe ,this probe hybridizes to chromosome 22 at band(q12,2)(spectrum
green on the centrometric side and spectrum orange on the telomeric side of the
EWSR1 gene breakpoint),total of 200 interphases were analyzed in this study, split signals were observed in
73% of the interphases indicating EWSRI gene rearrangement positive cells.
The patient was then started
on chemotherapy according to Ewing sarcoma protocol
(children’s oncology group) by
using alternating vincristine 2mg/m^2 D1 -doxorubicin 37.5mg/m^2
D1,2-cyclophosphamide 1200mg/m^2 D1 and ifosfamide 1800mg/m^2 D1-D5-etoposide
100 mg/m^2 D1-D5 cycles, two weeks between cycles for 14 cycles ,with
filgrastim(5mg/kg/day)between cycles .
primary tumor treatment with surgery and
radiation begin at week 13 after cycle 6
radiation doses was 45 Gy.
Figure (1a and 1b): Abdominal CT with contrast showing well-defined mixed
density soft tissue mass lesion measuring 78*62 mm arising from the upper pole
of the right kidney with no venous invasion.
Figure 2: Abdominal CT Postoperatively
with radical right-sided nephrectomy.
Figure 3: CT CHEST showed no distant metastasis
Figure 4:
A: Ewing sarcoma/PNET within
the kidney with adjacent glomeruli. Hematoxylin and Eosin stain.
200X
B: Ewing sarcoma/PNET with
rosetting. Hematoxylin and Eosin stain. 400X
C: CD99 positive in the tumor
cells. Immunohistochemical stain. 400X
D: Vimentin focal positive.
Immunohistochemical stain. 400X
Outcome and follow up: no
complications appeared during and or post-operation. The patient was started on
chemotherapy 10 days after wound healing according to the protocol, and
radiotherapy to the tumor bed for local control of the disease and to prevent
relapse was done.
2 Years follow up was
uneventful for new masses or recurrence.
DISCUSSION
Renal Ewing sarcoma tumor is a
rare entity in children. It usually presents in adults and a few cases have
been reported in children (3-5). Majority
of the patients affected by of ES of the Kidney are in their second and third
decades of life. Approximately 60% of those affected are male. Patients’
signs and symptoms mimic that of kidney stones including flank pain (84%),
palpable neoplasm (60%), and hematuria (38%) (6).
The cases reported worldwide
are 10 cases considering the pediatric age group below 15 years of age (7-10).
Ewing sarcoma of the kidney
(ESK) is a rare primary tumor of the kidney and can be mistaken with other
round cell tumors, like Wilms tumor blastema predominant. Around 90% of Ewing
sarcoma of the kidney have a specific t(11;22), which results in a chimeric
EWS-FLI-1 protein. ES of the kidney needs to be differentiated from other small
round cell tumors of the kidney because each type of tumor is treated
differently. Ewing sarcoma has diagnostic genetical findings. The most common
translocation is t(11; 22) (q24; q12) with EWSR1-FLI1 gene fusion (> 90%) (11-12).
We have to differentiate between the two entities as the prognosis is different
and each has a distinct treatment modality. For the diagnosis of Ewing sarcoma,
the morphological characteristics, immune-histochemical results, and genetic
studies are crucial for the diagnosis.
Metastasis was present in 66%
of patients at diagnosis with the lungs being the most common site of
metastasis in this tumor. Because of its poor prognosis and aggressive course,
establishing ESK for diagnosis is important for treatment and follow-up.
Diagnosis is usually done after resection of such a tumor. CT scan findings are
not specific for the type of renal tumor. Also, the microscopic findings in
such tumors are non-specific, so, the cytogenetic analysis and the
immunohistochemistry are needed for definitive diagnosis. In around (85 - 90)
percent of cases of Ewing sarcoma family tumors, a recurrent chromosomal
translocation, t(11;22) (q24;q12), fuses the 5' portion of the EWSR1 gene on chromosome 22 to the 3'
portion of the FLI1 gene on
chromosome 11. This can be detected using fluorescence in situ hybridization
(FISH).(13-14)
There is no specific approach
to the treatment of Ewing sarcoma of the kidney. Nephrectomy (surgical
resection of tumor) with adjuvant or neoadjuvant chemotherapy and radiotherapy
is the main management of such tumors.
The reported survival rate of
such patients was 26 months in the non-metastatic tumor while 5.6 months in the
case of metastasis.
CONCLUSION
Ewing sarcoma of the kidney is
an extremely rare tumor in children with the importance of differentiating this
type of renal tumor from other types as it has a more aggressive course with
inferior prognosis in comparison to other tumors. Although a multimodality
approach is helpful, survival rate is mostly limited to 1 year.
The earlier diagnosis with
non-metastasis at the time of diagnosis gives more rewarding results.
Reporting such cases will help
in the documentation of the treatment used and the outcome of our treatment
results to improve survival in such tumors.
REFERENCES
1. Seemayer T., Thelmo W., Bolande R. Peripheral neuroectodermal tumors. Perspect. Pediatr. Pathol. 1975;2:151–172. [PubMed] [Google Scholar]
2. Parham D., Roloson G., Feely M. Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the national Wilms’ tumor study group pathology center. Am. J. Surg. Pathol. 2001; 25:133–146. [PubMed] [Google Scholar]
3. Citak EC, Oguz A, Karadeniz C, Arzu Okur A, Akyurek N. Primitive neuroectodermal tumor of the kidney in a child. J Ped Hematol Oncol 2009; 26:481-6.
4. Ali SA, Muhammad AT, Siddiqui AJ. Extraosseous primary Ewing’s sarcoma. J Ayub Med Coll Abbottabad 2010; 22:228-9.
5. Badar Q, Ali N, Abbasi N, Ashraf S, Karsan F, Hashmi R. Ewing's sarcoma/PNET of kidney in a 13-year-old girl. J Pak Med Assoc 2010; 60:314-5.
6. Mohammed Hasen A. Alghamdi Saud Abdullah Alawad Mohammed Ghazi Alharbi Abdulrahman K. Alabdulsalam Fayez Almodhen Ahmed Alasker, “A rare case of Ewing’s sarcoma of the kidney,” Urology Case Reports, 29 (2020).
7. Ng AWH, Lee PSF, Howerd RG. Primitive neuroectodermal kidney tumor. Austral Radiol 2004; 48:211-3.
8. Vicha A, Stejskalvo E, Sumerauer D. Malignant peripheral primitive neuroectodermal tumor of the kidney. Cancer Genet Cytogenet 2002; 139:67-70.
9. Alonso AH, Gárate MM, Amo FH, Iribarren IM, Escudero RM, Sánchez JP, et al. Primary renal Ewing's sarcoma. Arch Esp Urol 2011; 64:636-9.
10. Alonso AH, Gárate MM, Amo FH, Iribarren IM, Escudero RM, Sánchez JP, et al. Primary renal Ewing's sarcoma. Arch Esp Urol 2011; 64:636-9.
11. Turc-Carel, Philip I, Berger MP. Chromosome study of Ewing's sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22) (q24;q12). Cancer Genet Cytogenet 1984; 12:1-19.
12. Berg T, Kalsaas AH, Buechner J, Busund LT. Ewing’s sarcomaperipheral neuroectodermal tumor of the kidney with a FUSERG fusion transcript. Cancer Genet Cytogenet 2009; 194: 53-57.
13.Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumors. Nature 359, 162–165 (1992).
https://doi.org/10.1038/359162a0
14.Zucman J, Delattre O, Desmaze C, Plougastel B, Joubert I, Melot T, Peter M, De Jong P, Rouleau G, Aurias A, et al. Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints. Genes Chromosomes Cancer. 1992;5(4):271-277