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2011, Volume 27, Number 2, Page(s) 110-115
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DOI: 10.5146/tjpath.2011.01058 |
CD138 Expression in Renal Tumors and Its Usage in the Differential Diagnosis |
Ayhan ÖZCAN1, Ertuğrul ÇELİK1, Yıldırım KARSLIOĞLU1, Şeref BASAL2 |
1Department of Pathology, Gülhane Military Medical Academy, School of Medicine, ANKARA, TURKEY
2Department of Urology, Gülhane Military Medical Academy, School of Medicine, ANKARA, TURKEY |
Keywords: Renal neoplasms, Syndecans, Immunohistochemistry, Differential diagnosis |
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Objective: The differential diagnosis of kidney tumors, especially those
with eosinophilic cytoplasms, can be problematic due to overlapping
morphologic features. CD138 is primarily a plasma cell marker but
is known to be expressed in the proximal renal tubular epithelium
as well. This study aims to investigate the possible contribution of
CD138 expression in the differential diagnosis of kidney tumors with
eosinophilic cytoplasm.
Material and Method: The case series consisted of 15 chromophobe
(ChRCC), 5 eosinophilic variant (EoRCC), 10 clear cell (CCRCC)
and 9 papillary (PRCC) renal cell carcinomas, and 13 oncocytomas.
Sections obtained from representative paraffin blocks were stained
against CD138 antibody.
Results: All CCRCC and PRCC showed membranous CD138
expression. In some of the other eosinophilic renal tumors,
cytoplasmic CD138 labeling in varying degrees was detected. In
CCRCC cases, CD138 expression was especially observed in low
grade areas and areas showing cystic and pseudopapillary growth
patterns. A similar pattern of cytoplasmic staining was seen in 3 of
the EoRCC and the most of the PRCC cases (6/9).
Conclusion: Our findings suggest that CD138 may contribute to the
differential diagnosis of renal tumors because of the membranous
staining pattern in CCRCC and EoRCC cases and the cytoplasmic
staining in CHRCC and oncocytoma cases. Its contributory role may
be improved by combined usage with markers like Cytokeratin 7 and
RCC marker. |
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Renal cell carcinoma (RCC) is the most common malignant
renal tumor. The 2004 WHO classification is used for the
diagnosis 1. The differential diagnosis of renal tumors, and
especially those with eosinophilic cytoplasm, can be difficult
due to overlapping morphological features. This problem can become more acute with small biopsies and when
metastases are being evaluated. Immunohistochemical
and sometimes electron microscopic investigations are
therefore frequently needed. Many immunohistochemical
markers such as cytokeratin subtypes, CD10, VHL protein, epithelial membrane antigen (EMA), paralbumin, carbonic
anhydrase, vinculin, CD24, hypoxia-induced factors (HIF
1α and 2α), “renal cell carcinoma marker antigen” (RCCM),
“kidney-specific cadherin” (KSC), GLUT-1 and PAX-2 have
been studied to this end 2-13. Most of these markers can
be expressed in tumors other than RCC as well and their
specificity is therefore limited. The contribution of RCCM
and KSC has been found to be higher than other markers
regarding a contribution to the diagnostic algorithm 8-11.
Similarly, PAX-2 has been reported to be more sensitive
than RCCM and KSC. Using these three markers together
has also been reported to be potentially helpful 13.
CD138 (Syndecan 1) is a 220-kDa adhesion molecule
that plays a role in the differentiation of B lymphocytes to
plasma cells. Syndecan 1 is expressed in epithelial cells and
Syndecan 2 in mesothelial and mesenchymal cells. CD138
is primarily a plasma cell marker but it has also been shown
to be present in the proximal renal tubules14. There
are only a few studies showing the presence of CD138
expression in RCC15,16. Our study aimed to investigate
the contribution of CD138 expression in the differential
diagnosis of renal tumors with eosinophilic cytoplasm. |
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Abstract
Introduction
Methods
Results
Disscussion
References
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The case series consisted of 15 chromophobe (CrRCC),
5 eosinophilic variant (EoRCC), 10 clear cell (CCRCC)
and 9 papillary (PRCC) renal cell carcinomas and 13
oncocytomas. All cases were reviewed for diagnosis
confirmation. Sections from the selected blocks were
stained with the CD138 marker (Neomarkers, Labvision,
Ab1, clone 5F7, 1:20, avidin-biotin-peroxidase) on an
automatic device (Ventana, Benchmark XT).
The presence of membranous and/or cytoplasmic staining
in at least 5% of tumor cells was interpreted as positive.
The staining intensity was graded and recorded semiquantitatively
as 0 (no staining), 1+ (weak), 2+ (moderate)
and 3+ (strong). The proximal renal tubules in the kidney
parenchyma neighbouring the tumor were used as positive
control.
Data obtained from the staining were evaluated with the
Chi square test. A p value <0.05 was accepted as statistically
significant. SPSS for Windows, ver. 16.0 (SPSS Inc., IL,
U.S.A.) was used for statistical evaluations. |
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Abstract
Introduction
Methods
Results
Disscussion
References
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The CD138 expression rates of the kidney tumors in our
series are presented in Table I. Most cases had a dominance
of membranous pattern and smaller rates of cytoplasmic
staining pattern.
Membranous staining:
All CCRCC cases had typical diffuse and strong (2+/3+)
membranous CD138 expression (Table I). CD138 expression
varied in diffuseness (in 5-75% of tumor cells) in CCRCC
cases. A stronger (3+) expression level in low-grade, cystic
and pseudopapillary areas was noted in CCRCC cases
(Figure 1A, B). One CCRCC case had no CD138 staining in
the sarcomatous area while there was strong membranous
staining in the low-grade clear cell areas. Most PRCC cases
(6/9) and only 3 EoRCC cases showed membranous staining
(Figure 2A, B, 3). The membranous CD138 expression in
these cases was at varying rates between 5% of tumor cells
and almost all. Only one PRCC case had type 2 morphology
and almost all areas showed strong cytoplasmic and
occasional membranous CD138 expression (Figure 2B).
Click Here to Zoom |
Figure 1: Membranous staining that is low-grade (A) and found in cystic and pseudopapillary (B) areas in a CCRCC case. |
Click Here to Zoom |
Figure 2: Membranous (A) and membranous and cytoplasmic CD138 expression (B) in PRCC. |
Cytoplasmic staining:
Other renal tumors with eosinophilic cytoplasm (CrRCC
and oncocytoma) showed cytoplasmic staining at varying
rates (5-95% of tumor cells) and intensity (Table I).
Cytoplasmic staining was generally more focal and weak
in CrRCC and more diffuse and strong in oncocytomas
(Figure 4, 5). However, membranous CD138 expression
was not seen in any of these cases.
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Top
Abstract
Introduction
Methods
Results
Disscussion
References
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Renal cell carcinoma is the most common malignant
tumor of the kidney. The morphological findings in
Hematoxylin-Eosin stained sections are generally adequate
for a categorical diagnosis. However, an overlap of these
morphological findings may create a problem in the
differential diagnosis in renal tumors with an eosinophilic
cytoplasm. Many immunohistochemical markers have
been studied to overcome this problem 2-13. However,
the specificity and sensitivity of these markers vary.
Markers such as CK7, RCCM and KSC have been reported
to be more sensitive for differential diagnosis 8-11. There
are still rare cases where the immunohistochemical panels
containing these markers can prove to be inadequate. The
need for the investigation of new immunohistochemical markers and their usage in pathology practice therefore
continues.
CD138 is a plasma cell marker and is mostly used in panels
directed towards hematopoietic malignancies. It is known
to be present in the proximal renal tubule epithelium14.
Our study results reveal the presence of CD138 expression
in a membranous or cytoplasmic manner in various
histological types of renal tumors with an eosinophilic
cytoplasm. Various renal tumor studies have used various
thresholds (such as 1%, 10%, 25%, 50%) for staining rates,
often without providing a rationale, when evaluating
immunohistochemical staining with various markers and
disregarded any staining below these threshold values.
However, the general tendency seems to be accepting any
staining of 10% or more of the target cell population as
positive10-12. We found that more than 5% of tumor
cells were stained with CD138 in almost all cases in our
study. The staining was less than 5% in only a few cases.
We therefore accepted 5% as the lower limit of significant
staining.
Chu et al. have found a CD138 expression of 63% in
renal cell carcinomas in a series consisting of a total of
447 hematopoietic and non-hematopoietic tumors15.
Similarly, O'Connell et al. have reported the expression
of CD138 in one renal cell carcinoma case in their series
of 238 hematopoietic and non-hematopoietic tumors16. The number of renal cell carcinomas was low in
both studies and there is no information on comment
on the quality, quantity or morphological pattern of the
staining. Our study found membranous and/or cytoplasmic
staining in 74% (29/39) of renal cell carcinomas and only
membranous CD138 expression in 49% (19/39). There was
a cytoplasmic staining pattern with various rates (5-95%
of tumor cells) and density (weak-strong) in CrRCC and
oncocytoma cases. RCC cases other than CrRCC showed
diffuse and strong membranous staining in tumor areas,
especially in low-grade areas and those with a dominant
cystic, pseudopapillary or papillary growth pattern. The
sarcomatoid area in one of these cases did not show CD138
immunoreactivity, in contrast to the surrounding areas. The
tumor cells with eosinophilic cytoplasm seen in CCRCC
cases generally showed cytoplasmic and only focal CD138
immunoreactivity. Membranous staining was less common
and discontinuous. Some EoRCC and one type 2 PRCC
case in our series showed moderate to marked cytoplasmic
staining despite the low rates of membranous staining.
The Chi-square test performed by taking into account
whether the CD138 expression was mainly membranous
or cytoplasmic revealed that this pattern difference was limited to some histological subtypes in general and that
the difference was statistically significant (p=0.003) (Table I).
Our study aimed to show the expression of CD138, mainly
a plasma cell marker, in renal tumors and its possible
contribution to the differential diagnosis. It is the most
comprehensive of similar studies in the current and
accessible literature. CD138 mainly shows a membranous
staining pattern in renal tumors while a cytoplasmic
pattern is less frequent and more faint. Consideration of
the histological subtypes revealed that CD138 showed
a membranous staining in CCRCC, PRCC and EoRCC
cases and a cytoplasmic staining pattern in CrRCC and
oncocytoma cases. It is noteworthy that tumors with a
membranous staining pattern are of proximal nephron
origin while those with a cytoplasmic staining pattern are
of distal nephron origin. This difference that has not been
noted or emphasized in other studies may possibly be a
reason for using CD138 for the differential diagnosis of
renal tumors. |
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Abstract
Introduction
Methods
Results
Discussion
References
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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