D R P R A S H A N T H A D I G A K

PRIMARY NEURECTOERMAL

TUMOR OF KIDNEY

INTRODUCTION

Primitive neuroectodermal tumors (PNET) are a group of

small round cell malignancies with neural crest origin.

They are highly aggressive and rare.

These tumors may originate in the central nervous system

or in other tissues peripherally.

The peripheral type is seen typically in the soft tissues of

the chest wall and paraspinal region and unusually along

the genitourinary tract

INTRODUCTION

PNET rarely presents as an organ-derived neoplasm.

The overall incidence of peripheral PNET is 1% of all sarcomas.

The incidence of PNET in the abdomen and pelvis, including the retroperitoneum, is about 14% of all peripheral PNETs.

Renal PNET is extremely rare with fewer than 50 cases in the literature

INTRODUCTION

EWS/PNET occurs rarely as a primary renal neoplasm

and exhibits highly aggressive biological behavior.

Most patients are young adults with a median age of 28

years (range 4 to 69) and a slight male predominance

(1.5:1).

Because of their morphological resemblance to

neuroblastomas, they have been considered to be neural

crest derivatives

FACTS

Until now, the largest series of rPNET was published

by Yuvaraja B and al. This series included 16 patients

who were treated in Tata Memorial Hospital in India

ORIGIN

The origin of this tumor is unknown, but it seems that

it derives from cells that migrated from the neural

tube, with variable capability of ectodermal or

neuronal differentiation.

SIGNS AND SYMPTOMS

The presenting symptoms and images of rPNET are non-

specific and similar to other renal tumors.

Therefore it is often difficult to distinguish rPNET from

renal cell carcinoma and Wilm’s tumor.

The clinical symptoms and signs are nonspecific,

comprising flank or abdominal pain, palpable mass and

hematuria in decreasing order.

SIGNS AND SYMPTOMS

rPNET appears to be an unique clinical entity that behaves

more aggressively than PNET arising at other sites.

Approximately 20% to 50% of patients present with

distant metastases, most commonly to regional lymph

nodes, bone, bone marrow, lung, and liver.

The 5-year disease-free survival rate of rPNET is about

45% to 55%

Lab findings

Laboratory findings are mostly unremarkable but

increased lactate dehydrogenase is sometimes reported.

RADIOLOGY

Radiographic features of PNETs are large size, lack of

extensive parenchyma infiltration, lack of renal vein

invasion, diffuse large calcification, areas of internal

hemorrhage and necrosis, and peripheral hypervascularity

Histological examination

A small rounded cell tumor with hyperchromatic nucleus

and scant cytoplasm in a fibrotic stroma.

Immunohistochemical finding was compatible with PNET

or Ewing’s sarcoma (positive for neuron specific enolase

(NSE), vimentin, CD99 and negative for desmin,

leukocyte common antigen (LCA) and chromogranin)

D/D

Carefully selected immunohistochemical panel is

important for differentiating this tumor from other small

round cell tumors of the kidney such as

Rhabdomyosarcoma,

Neuroblastoma,

Clear cell sarcoma of the kidney,

Desmoplastic small round cell tumor (DSRCT),

Carcinoid tumor,

Nephroblastoma

Ewing’s sarcoma

IMMUNOHISTOCHEMISTRY

Immunohistochemically, PNET cells express vimentin, NSE and CD99.

The positive reactivity to CD99 is a clue for PNET diagnosis.

MIC2 gene product (a monoclonal antibody that recognizes the glycoprotein p30/32 MIC2) which has fairly recently been introduced, is reported to show immunoreactivity in 90%-95% of Ewing’s sarcoma and PNET

IMMUNOHISTOCHEMISTRY

The cloning of the breakpoints of the specific

chromosomal translocations t (11; 22)(q24; q12) and t

(21; 22)(q22; q12) that are present in approximately

90% of PNET/Ewing’s sarcomas permits the use of the

reverse transcription polymerase chain reaction (RT-

PCR) for the detection of specific fusion transcripts in

these tumors.

The rosette-like structures formed by the small monotonous round cells

The tumor cells showed strong positive expression of CD99.

The tumor cells showed positive expression of S-100.

The part of tumor cells showed positive expression of NSE.

PATHOLOGY

The diagnosis of rPNET mainly depends on pathologic

characteristics and biomarkers.

rPNET is characterized by small uniform round cells with

dark nuclei, illdefined cytoplasmic borders, and poorly-

formed rosettelike structures.

Additionally, CD99 also named MIC-2 antigen is crucial

in the diagnosis of rPNET and the positive expression of

CD99 has been demonstrated in more than 90% of rPNET

PATHOLOGY

CD99 is not specific and cannot be used as an absolute

biomarker.

Cytogenetic analyses may therefore be helpful in the

diagnosis of rPENT.

The translocation of t(11:22) (q24:q12) with the fusion

transcript between the EWS gene (22q12) and the ETS-

related oncogene (11q24) have been detected in more than

90% of patients

CD99

synovial sarcoma,

Wilms’ tumor,

vascular malignancy,

neuroendocrine tumors,

lymphoblastic lymphoma

WILMS TUMOR

• The features favoring the diagnosis of blastemal Wilms

tumor are young age and positivity of blastemal elements

for vimentin, low molecular weight cytokeratin, epithelial

membrane antigen, and WT1.

• Immunohistochemistry is very useful to differentiate it

from renal primitive neuroectodermal tumor/EWING

tumor because neuroblastomas are consistently positive

for NSE and chromogranin and mostly negative for

CD99.

TREATMENT

Surgical excision remains the most important modality of

management which has shown the survival advantage.

Despite aggressive treatment of these tumors by

combination therapy with surgery, chemotherapy, and

radiotherapy, the prognosis remains poor and overall 5-

year survival rates have been reported at 45% to 55%.

TREATMENT

Before the routine use of adjuvant chemotherapy, the 5-

year survival rate in patients with rPNET was less than

10%.

Cyclophosphamide (C), actinomycin (A), and vincristine

(V) were found to be effective in this group of diseases.

Later, it was demonstrated that doxorubicin (D) was also

an active agent.

TREATMENT

The most recent additions to the list of active agents in

this disease have been ifosfamide (I)and etoposide (E).

The addition of latter 2 drugs to the previous standard

treatment of VAC alternating with VCD has been shown

to improve the overall and disease-free survival in patients

with nonmetastatic skeletal Ewing’s sarcoma

TREATMENT

The use of dose-intensive combination regimen lasting

about 49 weeks is the std.

At TMH institution they have used these 6 drugs in EFT-

2001 protocol.

Because of the high incidence of febrile neutropenia, all

patients receive prophylactic granulocyte-colony

stimulating factor (G-CSF) after courses.

EFT-2001 protocol

RADIATION

Radiation therapy is useful in treating these patients,

especially when the resection is not possible or residual

disease is present.

It is logical to give radiotherapy in the presence of

Gerota’s fascia involvement and positive surgical margins.

Radiation dose varied from 5040 to 6000 rads

TREATMENT

Thomas et al.24 and Karnes et al.25 have described a case

of PNET kidney associated with IVC thrombus which was

removed at the time of nephrectomy

Radical nephrectomy was immediately done based on the findings of CT of the right

kidney.

rPENT who immediately underwent six cycles of chemotherapy with ifosfamide,

etoposide, and adriamycin.

KEY POINTS

The preferred treatment for rPENT is surgical resection

associated with chemotherapy and radiotherapy treatment.

The role of radiotherapy is not clear, but it may be

advocated in locally advanced disease and involvement of

Gerota’s fascia.

Most cases of rPNET may recur after nephrectomy

without adjuvant chemotherapy.

CONCLUSIONS

PNET are small round cell tumors of presumed neural

crest origin arising outside the central and sympathetic

nervous system.

PNET of the kidney is a distinct clinical entity with

aggressive behavior.

The tumor diagnosis is based on a classical histologic and

IHC features complemented by cytogenetics and

molecular analysis.

CONCLUSIONS

Aggressive multimodality treatment is recommended to manage these tumors.

Complete resection of the kidney with node dissection should be performed if at all feasible.

The best results are seen with combination chemotherapy that is used for other round cell tumors like Ewing’s sarcoma

The role of radiotherapy is not clear but may be advocated in locally advanced disease and involvement of Gerota’sfascia