Yetişkin blastemal Wilms tümörüne benzerlik gösteren renal primer primitif nöroektodermal tümörün immünohistokimyasal özellikleri: olgu sunumu

PDF Dosyası: 

arastirmax_1623_pp_112-115.pdf

Introduction
Primary primitive neuroectodermal tumor (PNET) is
a rare primary tumor of the kidney that resembles other malignant small round cell tumors of assumed neuroectodermal origin (1-13). The differential diagnosis
of the poorly differentiated small round cell tumors
of the kidney includes PNET, blastemal Wilms tumor,
neuroblastoma, rhabdomyosarcoma, lymphoma, clear
cell sarcoma, synovial sarcoma, desmoplastic small
round cell tumor and small cell carcinoma. It is essential because of their different therapeutic and prognostic implications. The most common primitive tumor
in kidney, Wilms tumor, responds well to a standard
protocol of multidrug chemotherapy (4), whereas primary renal PNET has an aggressive clinical course that
requires more extensive therapy, which includes radiotherapy and multidrug chemotherapy (5).
While immunohistochemical panel may be valuable in the differential diagnosis of renal small round
cell tumors, the differential diagnosis may still be
problematic because of the presence of overlapping
morphologic and immunophenotypic features in
some cases. Especially, the discrimination of PNET
and blastemal Wilms tumor in kidney may be difficult, when both CD99 and WT1 expression are detected. We report a rare primary renal PNET showing
both CD99 and WT1 expression.
Case Report
A 44-year-old man admitted to our hospital with left
flank discomfort. The clinical symptoms did not subside with anti-inflammatory agents. Several months
later, he admitted to the nephrology department
with hematuria and elevated serum creatine level.
Abdominal axial non-contrast computed tomography
scan showed a large hypodense solid mass measuring
16x12.5x11 cm in the left kidney with a large lymph
node at the medial aspect of the mass, pushing the
aorta to the right (Figure 1). Normal left kidney paren-
* Department of Pathology, Gülhane Military Medical Faculty
Reprint request: Dr. Ayhan Özcan, Department of Pathology, Gülhane
Military Medical Faculty, Etlik-06018, Ankara, Turkey
E-mail: aozcan06018@yahoo.com
Date submitted: February 18, 2008 • Date accepted: April 24, 2008Volume 51 • Issue 2 Renal primary primitive neuroectodermal tumor • 113
chyma was not distinguished, and the aorta and vena
cava inferior appeared normal in computed tomography. The patient underwent left radical nephrectomy.
There was no metastasis to any other organs in clinical screening tests performed after pathology report.
Adjuvant multidrug chemotherapy and radiotherapy
were planned as further treatment procedures.
tumor demonstrated lobular growth pattern with multiple areas of hemorrhage and necrosis. Tumor thrombus was detected inside the renal vein and measured
5x4x1.5 cm in dimension. The tumor invaded perirenal fat tissue and extended to the adjacent adrenal
gland.
Microscopically, the tumor was arranged in lobules
with different sizes, and composed of diffusely proliferating uniform population of blue round small cells
(Figure 3). These cells formed sheets, true HomerWright rosettes and pseudorosettes were readily identified. The tumor cells had regular nuclear contours,
Figure 1. Abdominal axial non-contrast computed tomography scan
revealed a large hypodense solid mass (white arrows)
Macroscopically, the left kidney and the adrenal
gland with perirenal fat measured 18x17x8.5 cm. The
kidney was entirely replaced with a solid gray tumor
measured 16x12.5x11cm in diameter (Figure 2). The
Figure 2. Macroscopic appearance of primary renal primitive
neuroectodermal tumor
Figure 3. The tumor was composed of blue small round cells.
Perivascular pseudorosettes and rosettes were readily identified
(H&E, x100)
finely dispersed chromatin without prominent nucleoli, and eosinophilic scanty cytoplasm. The tumor
showed extensive necrosis and numerous mitotic figures. There was no evidence of any epithelial or blastema like component while numerous sections were
examined. The tumor extended to the adjacent adrenal gland without invasion. Tumor thrombus was
identified in the lumen of the renal vein. There was
also perirenal lymph node metastasis and perinodal
infiltration in the same lymph node.
Immunohistochemistry was performed on formalin-fixed, paraffin embedded tissue using the
usual avidin-biotin-peroxidase complex method.
Antibodies used in immunohistochemical study and
their results are summarized in Table I.
The tumor cells were diffuse strong positive for CD99
(membranous pattern) (Figure 4A), and NSE (cytoplasmic pattern), focal positive for WT1 (nuclear pattern)
(Figure 4B), diffuse weak positive for synaptophysin
(cytoplasmic pattern). The tumor cells were negative
for LCA (CD 45), CD 56, TTF-1, pancytokeratin, cy-114 • June 2009 • Gulhane Med J Özcan et al.
tokeratin 7 and 20, vimentin, desmin, smooth muscle
actin (SMA), S-100 protein and chromogranin A.
Discussion
PNET was first described by Arthur Pourdy Stout in
1918. The most common locations are in the soft tissue of the trunk, extremities, head and neck. The first
primary renal PNET was reported by Mor et al (6).
There are very few cases and most of them are case
reports in the literature (1-13). Primary renal PNET
is a rare entity that behaves more aggressively than
PNET arising at other sites. The disease occurs predominantly in children and young adults. Primary
renal PNET has a high recurrence rate and a tendency
to metastazing to renal vein, regional lymph nodes,
lungs, liver, bone and bone marrow at early stages.
The distinction from other primary small round cell
tumors of the kidneys is essential for prognosis and
therapeutic modalities. Especially, the differential diagnosis between renal PNET and blastemal WT may
be problematic because of overlapping histopathological and immunophenotypical features.
Primary renal PNET may present with non-specific
findings and its radiological differential diagnosis
from other more frequent primary and metastatic renal tumors may be difficult. Small round cell tumors
of the kidney histopathologically and closely resemble the other primitive tumors and the more common
counterpart in soft tissue. Immunohistochemical
positivity for CD99, NSE, and FLI-1 are very helpful
in differential diagnosis of PNET and other primitive
small round cell tumors (7,8). Chromogranin A and
synaptophysin are negative or weak positive in PNET
(1). Although vimentin is usually positive in PNETEWS (1-13), it is more often positive in Ewing sarcoma than in PNET. Some studies suggest that vimentin may be negative in PNET as in the present case
(9-12). Pan-cytokeratin is negative, while it is positive in approximately 20% of CD99 positive primary
renal PNET cases (1,7). Pan-cytokeratin positivity is
meaningful for small cell carcinoma, when there is
no CD99 expression. CK7 and CK20 expression patterns and TTF-1 expression are useful for the distinction of metastatic Merkel cell carcinoma and primary
or metastatic small cell carcinoma. Homer–Wright
rosettes, positivity for NSE, chromogranin A and synaptophysin are more typical for neuroblastoma than
PNET-EWS. LCA (CD45) immunoreactivity is characteristic for lymphoma. CD56 is negative in PNET
as in the present case, while it is positive in neuroblastoma, neuroendocrine tumors, small cell carcinoma and Merkel carcinoma. Rhabdomyosarcoma
is typically immunoreactive for actin, desmin, MyoD1 and myogenin, while they are negative in PNET.
Desmoplastic small round cell tumor was immunoFigure 4. A. Membranous CD99 expression. B. Focal nuclear WT1
expression (Immunohistochemistry)
Table I. Antibodies used in immunohistochemistry and immunohistochemical results
Antibody Dilution Vendor Results
CD99
WT1
NSE
Synaptophysin
Chromogranin A
S100
LCA (CD45)
Smooth muscle actin
Desmin
Pan-cytokeratin
Cytokeratin 7
Cytokeratin 20
CD 56
TTF-1
1:100, monoclonal
1:25, monoclonal
1:100, monoclonal
1:100, monoclonal
1:100, monoclonal
1:100, monoclonal
1:100, monoclonal
1:100, monoclonal
1:50, monoclonal
1:100, monoclonal
1:100, monoclonal
1:50, monoclonal
1:80, monoclonal
1:20, monoclonal
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
Neomarkers, Fremont, CA
+, diffuse
+, focal
+, diffuse
+, diffuse
-
-
-
-
-
-
-
-
-
-Volume 51 • Issue 2 Renal primary primitive neuroectodermal tumor • 115
reactive for vimentin, WT1, desmin, NSE, pan-cytokeratin, and epithelial membrane antigen (13). CD99,
synaptophysin and chromogranin were focally immunoreactive in desmoplastic small round cell tumor. We ruled out the possibility of the desmoplastic
small round cell tumor, as desmin and pan-cytokeratin were negative.
The most challenging differential diagnosis is between PNET and blastemal Wilms tumor (7). The WT1
protein is encoded by the WT1 gene located on chromosome 11p13. This gene is required in tissue differentiation and proliferation. WT1 has been used as a
discriminative immunohistochemical marker for the
diagnosis of Wilms tumor. It shows normally nuclear
expression in the glomerular podocytes, mesothelial cells and stem cells. The blastemal component of
Wilms tumor usually shows strong immunoreactivity
for WT1. This immunoreactivity may have potential
in discrimination other primitive small round cell
tumors from blastemal Wilms tumor that might be
diagnostically challenging with PNET. Jimenez et al.
demonstrated WT1 immunoreactivity in 7 of 9 Wilms
tumors while all PNET cases were negative (7,14).
While diffuse and strong CD99 (MIC2 gene) expression was detected in PNET, it is usually not expressed
in Wilms tumor (1). However, CD99 expression can
be occasionally seen in Wilms tumor (7). Ellison et
al. reported both CD99 and WT1 expression in 7 of
30 primary renal PNETs (8). In the same study, FLI-1
was negative in 2 of these 7 cases. When both CD99
and WT1 expression are positive as in the present
case, the distinction of PNET and Wilms tumor may
be problematic. Nevertheless, diffuse strong membranous CD99 and focal nuclear WT1 expression have
supported to PNET rather than Wilms tumor. Diffuse
WT1 and focal CD99 expression may be interpreted
as Wilms tumor rather than PNET.
Primary renal PNET is a rare small round cell tumor. However differential diagnosis from other renal small round cell tumors is crucial because of
its distinctive clinical behavior and different therapeutic approaching. We reported a rare primary renal PNET showing both CD99 and WT1 expression.
Immunohistochemical study may be usually useful
in the differential diagnosis of these tumors. However
in some cases, histopathological and immunohistochemical features of the tumor may not be helpful
because of overlapping features. However, diffuse
strong CD99 expression seems to be still very effective in differential diagnosis of primitive small round
cell tumor, especially, in distinction of PNET and
Wilms tumor in kidney. The definitive differential
diagnosis of PNET and Wilms tumor which are both
still remain problematic despite immunohistochemical results should be supported with genetic, molecular and ultrastructural studies.