Primary Paediatric Renal Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature
Binny KHANDAKAR, Moumita MAİTİ, Soumit DEY, Prasenjit Sen RAY, Palas BHATTACHARYYA, Ranu SARKAR
Department of Pathology, Nil Ratan Sircar Medical College & Hospital, KOLKATA, INDIA
Keywords: Ewing sarcoma, Kidney, Primitive neuroectodermal tumor
Ewing sarcoma/primitive neuroectodermal tumor (PNET) is a high-grade malignant neoplasm commonly affecting bones of the thoracic region.
Primary Ewing sarcoma/PNET of the kidney is exceptional; it commonly affects young adults and is rarely reported in children.
Here we describe a case of renal PNET in a 10-year-old girl who presented at our institute with haematuria and abdominal lump. Computer
tomography scan revealed a huge mass in the right kidney. Computer tomography-guided aspiration from the mass showed cytomorphological
features of a small blue round cell tumor. The patient underwent right radical nephrectomy. Histopathology with supplementary
immunohistochemistry confirmed the diagnosis of PNET. She has been receiving treatment with adjuvant chemotherapy post-surgery and is
currently disease free.
Primary renal PNET is a distinct and rare entity. This tumor is very aggressive with low survival rate, even with a multi-disciplinary approach.
We reported the case because it is rare in children, poses diagnostic challenges, is aggressive in behaviour and responds poorly to treatment.
Primitive neuroectodermal tumor (PNET) is a malignant
neoplasm that originates from neural crest cells and the
neuroectoderm that are found during normal human
development. These tumors are broadly classified as central
(CNS PNET) and peripheral, which is also known as
Ewing sarcoma/primitive neuro-ectodermal tumor (ES/
PNET) due to its signature genetic alteration. ES/PNET is
primarily a bone-soft tissue neoplasm. Primary ES/PNET
of the kidney is an exceptionally rare malignant lesion1
. Median age of presentation is 27 years; it is extremely
uncommon in <15 years and only a few sporadic cases
have been reported so far2
. Conclusive diagnosis is
done by morphology, immunohistochemistry (IHC) or
molecular techniques. Patients are managed aggressively
with surgery, chemotherapy with/without adjuvant
radiotherapy. A commonly employed regimen includes
combination chemotherapy with vincristine, adriamycin,
cyclophosphamide (VAC) with alternating ifosfamide and
. Response to treatment is often poor
even with multimodality treatment. Overall prognosis and
survival is mostly bleak though younger patients often have
better survival than older ones4
. Here we report a case
of primary ES/PNET of the kidney in a 10-year-old female.
A 10-year-old girl presented with intermittent haematuria
for one week. Detailed clinical history revealed complaints
of right-sided abdominal discomfort and generalised
weakness for three months prior to the onset of haematuria.
Examination revealed a palpable mass in the right lumbar
region. Blood and urine examination showed mild anemia
and presence of RBCs in the urine. Urine culture was
negative. Serum creatinine was within normal limits.
Contrast-enhanced Computer Tomography (CECT)
Scan showed loss of normal right renal architecture and
replacement with a huge mass (10.44x9.02 cm), displaying
hyper-dense enhancing and hypo-dense non-enhancing
areas, without any excretion of contrast, suggesting a
neoplastic lesion (Figure 1A
). The left kidney was normal.
A CT-scan guided aspiration from the mass showed
cytomorphological features of a small blue round cell
tumor. The patient subsequently underwent right radical
Click Here to Zoom
|Figure 1: A) CECT image of right renal mass. B) Gross appearance of tumor with grey-white cut surface.
Grossly, the specimen measured 14.5x10x8 cm and weighed
700 gm. The cut surface showed that almost the entire renal
parenchyma was replaced by a solid, grey white tumor with
areas of haemorrhage, necrosis, and cystic degenerations (Figure 1B). Multiple sections examined from the tumor
showed tumor cells arranged in diffuse solid sheets, vaguely
separated by broad fibrous bands, interspersed with
perivascular pseudo-rosettes and haemorrhage at places
(Figure 2A-C). The individual tumor cells were small and
round with scanty vacuolated cytoplasm, and had round to
oval vesicular to hyperchromatic nuclei, evenly dispersed
granular chromatin, inconspicuous nucleoli and frequent
mitosis. Large areas of necrosis and occasional lymphovascular
emboli were also seen (Figure 2D). The renal sinus
and perinephric fat showed involvement by the tumor,
though the resected end of the ureter and hilar vessels and
sampled lymph nodes were free of pathology. Periodic
acid–Schiff (PAS) stain for intracytoplasmic glycogen
revealed an occasional cell with minimal glycogen (Figure
2E). A provisional diagnosis of small blue round cell tumor,
possibly ES/PNET was made. A panel of IHC was ordered
for chromogranin (CG), neuron-specific enolase (NSE),
CD 99, Wilms' tumour (WT1), leukocyte common antigen
(LCA), cytokeratin (CK), myogenin, desmin. The cells
showed a strong and diffuse predominantly membranous
expression of CD 99 (Figure 2F) with focal positivity for
NSE; however the cells were immuno-negative for WT1,
CG. Other makers which were negative included LCA
(leukocyte common antigen), CK (cytokeratin), myogenin,
desmin. Based on morphology and IHC results, a final
diagnosis of renal PNET/ES was given. Molecular testing
for the EWS-FLI-1 fusion gene or IHC for FLI1 expression
could not be performed due to non-availability.
Click Here to Zoom
|Figure 2: A) Tumor cells in diffuse sheets (H&E; x40). B) Pseudo-rosette formation (H&E; x40). C) High magnification of pseudo-rosette
(white arrow) (H&E; x100). D) Lymphovascular invasion (black arrow) (H&E; x40). E) Minimal glycogen content in neoplastic cells
(black arrow) (PAS; x100). F) Neoplastic cells showing CD99 positivity (CD99; x100).
The patient had an uneventful post-operative period and
was subsequently referred to the department of Oncology-Radiotherapy for further management. She was started on
chemotherapy four weeks post-surgery and has completed
two cycles of chemotherapy without any obvious metastasis
PNET/ES covers one percent of all sarcomas5
. It is a
malignant small round cell tumor of neural crest origin,
first described in the ulnar nerve by Arthur Pourdy Stout
. Commonly, PNETs arise in the ribs and
paraspinal areas; involvement of skin, soft tissue, lungs,
kidney, and retroperitoneum is rare. Renal PNET was first
described almost sixty years later than the first report of
PNET, in 1975; few cases have been reported so far7
now, around 100 cases have been reported worldwide, with
very few from India8
Renal PNET commonly affects young adults, though the age
range is 4 - 61 years in reported cases. It more commonly
affects males, with a male to female ratio of 3:18. Most
cases of renal PNET are diagnosed on resected specimens,
based on histopathology and immunohistochemistry.
The differential diagnosis includes other small round cell
tumors, including Wilms' tumour, neuroblastoma, and
lymphoma. These tumors are composed of primitiveappearing
round cells with a high nucleo-cytoplasmic ratio.
Perivascular pseudo-rosettes are usually identified; Homer-
Wright rosettes are less frequently seen. A commonly
appreciated feature on electron microscopy is aggregates
of cytoplasmic glycogen granules though sometimes polar
processes, microtubules or neurosecretory granules are
seen, suggesting a neuronal differentiation9. Tumor cells express CD99 (MIC2) and FLI-1 with variable positivity for
neuroendocrine markers including NSE, synaptophysin,
and CG. WT1, a marker for Wilms' tumor, is not expressed
in PNET. A combination of markers is generally helpful
in arriving at the correct diagnosis. Eighty to ninety five
percent of the cases show t(11;22) (q24;q12) while the
remaining ones often display an EWS/Ets-related gene
(ERG) mutation10. Cytogenetic studies could not be
performed in our case because of non-availability.
Radiological findings of renal PNET are nonspecific and
commonly show a massive renal mass. Imaging finding
of the present case included a large contrast-enhancing
hyper- and hypo-dense mass without contrast excretion
through the pelvi-calyceal system with very thin residual
As in other sites, renal PNET is very aggressive and about
50% patients come with distant metastasis at presentation.
Common sites for metastasis are regional lymph nodes,
liver, and lung. Overall survival is low and most patients do
not live beyond one year following the diagnosis. Patients
are generally treated with a multi-modality approach;
radical nephrectomy with combination of chemotherapy
with drugs including vincristine, doxorubicin,
cyclophosphamide, etoposide and ifosfamide9. Adjuvant
radiation is given in patients with incomplete resection,
positive resection margins, or recurrence.
In conclusion, primary renal PNET is a distinct and rare
entity, typically affecting young adults. This tumor is
very aggressive with a low survival rate, even with multimodality
treatment. Although the incidence of renal PNET
in children is low, oncologists and pathologists need to be
aware of this tumor and every attempt should be made to
differentiate it from other more common tumors as it carries
very poor prognosis. Morphology alone can only suggest
PNET as an important differential of small round cell
tumors; ancillary techniques and immunohistochemistry
for CD99 with or without a molecular test are vital to
establish a correct diagnosis. We reported this case for its
aggressive nature and rarity in children.
1) Maeda M, Tsuda A, Yamanishi S, Uchikoba Y, Fukunaga Y, Okita
H, Hata J. Ewing sarcoma/primitive neuroectodermal tumor of
the kidney in a child. Pediatr Blood Cancer. 2008;50:180-3.
2) A ghili M, Rafiei E, Mojahed M, Zare M. Renal primitive
neuroectodermal tumor: Does age at diagnosis impact outcomes?
Rare Tumors. 2012;4:e15.
3) Giridhar P, Mallick S, Kumaran D, George A, Kaushal S, Julka
PK. Primitive neuro-ectodermal tumour of kidney in adult:
Report of four consecutive cases and review of the literature. J
Egypt Natl Canc Inst. 2015;27:235-8.
4) Jimenez RE, Folpe AL, Lapham RL, Ro JY, O'Shea PA,
Weiss SW, Amin MB. Primary Ewing's sarcoma/primitive
neuroectodermal tumor of the kidney: A clinicopathologic and
immunohistochemical analysis of 11 cases. Am J Surg Pathol.
5) Funahashi Y, Hattori R, Yamamoto T, Mizutani K, Yoshino Y,
Matsukawa Y, Sassa N, Okumura K, Gotoh M. Ewing's sarcoma/
primitive neuroectodermal tumor of the kidney. Aktuelle Urol.
6) Sout AP. A tumour of the ulnar nerve. Proc N Y Pathol Sco.
7) Seemayer TA, Thelmo WL, Bolande RP, Wiglesworth FW.
Peripheral neuroectodermal tumors. Perspect Pediatr Pathol.
8) Mandal PK, Mukherjee S, Roy S, Bhattacharyya NK. PNET of
kidney: Report of four cases. Indian J Med Paediatr Oncol.
9) Citak EC, Oguz A, Karadeniz C, Okur A, Akyurek N. Primitive
neuroectodermal tumor of the kidney in a child. Pediatr Hematol
10) Yang Y, Zhang L, Wei Y, Wang H, Xiong W, Chen Z, Hes
O, Zheng J. Detection of EWSR1 translocation with nuclear
extraction-based fluorescence in situ hybridization for diagnosis
of Ewing's sarcoma/primitive neuroectodermal tumor. Anal
Quant Cytol Histol. 2007;29:221-30.