Clusterin Expression Distinguish Follicular
Dentritic Cell Tumor From Other Dentritic
Cell Neoplasm: Report of a Novel
Follicular Dentritic Cell Marker and
Clinicopathologic Data on 12 Additional
Follicular Dentritic Cell Tumors and 6
Additional Interdigitating Dentritic Cell
Tumors
~2004AJSP August
Background(1)
• Tumor of dendritic cell lineage, including
follicular dendritic cell tumor(FDCTs),
interdigitating dentritic cell tumor(IDCTs)
and Langerhans cell histiocytoses(LCH),
are rare
• Share IHC positive for fascin, CD68 and
many morphologic features
Background(2)
• CD21, CD23, CD35,CD1a and S100
distinguish them
• D/D FDCTs and IDCTs is of clinical
importance
• CAN.42, Ki-FDC1p, Ki-M4p, R4/23 and
desmoplakin
Clusterin(1)
• Expression in benign follicular dendritic
cell
• Clusterin glycoprotein expressed in
parenchyma cells of liver, stomah and brain
• Complement fixation, membrane protection,
cell aggregation, cell-matrix interaction,
lipid transport, apoptosis, stress –induced
secreted chaperone protein
Clusterin(2)
• Expression in anaplastic large cell
lymphoma, diffuse large B cell lymphoma,
peripheral T-cell lymphoma, nodular
sclerosis Hodgkin lymphoma, ca of breast,
colon, pancreas, and prostate
• Expression on dentritic cell tumor has not
previously been reported
• Substantial number
Material and method(1)
• Mayo Clinic in-house and consutation file,
1995~2003
• Follicular dendritic cell sa/tumor, interdigitating
dendritic cell sa/tumor, dendritic cell,NOS
• FDCT: 20>>>> 12
• IDCT: 9>>>> 6
• DCT, NOS: 5>>>> 3>>>6
• LCH: 3+11
Material and method(2)
• Paraffin embedded tissue: CD21, CD23,
CD35, CD1a, S100, CD68, fascin and
clusterin were applied
• Selected case: additional IHC marker were
applied
• Positive of clusterin was scored both
quantitatively(0~4) and qualitatively
Material and method(3)
• EM was performed on selected case( 3
FDCT, 2 IDCT, 6 spindle cell tumor, NOS)
• Clinical data and f/u information were
obtained in FDCT and IDCT cases from
Mayo Clinic patient redords or discussion
with the referring physcians
Result
histological feature(1)
• FDCT: variable number of multinucleated
tumor cells, intermixed inflammatory cell,
centered in the cortical region of LN,
• Myxoid change, pseudovascular space,
dense fibrosis, angiofollicular hyperplasia,
necrosis
• Mitoses: 0~34/10 hpf(M: 11.4)
Result
histological feature(2)
• IDCT: greater degree of nulclear pleomorphism,
more polygonal cell with more abundant
eosinophilic cytoplasm
• Paracortical distribution
• 2 case: histiocyte like
• Intermixed lymphoplasmacytic population and
multinucleated tumor giant cell
• Mitose: 0~19/10 hpf (M: 7.5)
• necrosis
IHC(1)
• Clusterin diffuse strong cytoplasmic
staining in all FDCT
• Majority of FDCT showed positive for one
or more of the tranditional FDC marker
• CD1a and S-100 were negative in all FDCT
• CD68 and fascin were positive in the
majority
IHC(2)
• 2 case of FDCTs were negative of
CD21,CD23 and CD35, were classified as
FDCT by EM
• Negative for actin, desmin, ALK-1, CK,
CAM5.2
• Both show positive for EMA
IHC(3)
• IDCT: negative or showed only focal weak
positive for clusterin
• All IDCT were strongly positive for S-100,
fascin and negative for CD1a, CD21,CD35
• Subset case shows CD23 and CD68 positive
IHC(4)
• 6/14 LCH complete negative for clusterin
and 8 cases showed variable positive
• All LCH were positive for CD1a, fascin and
CD68
• S-100 showed variable intensity in 13 cases
• CD21,CD35 were negative in all cases
• CD23: equivocal in 9 cases
IHC(5)
• 6 spindle cell tumor, NOS: all showed some
degree of fascin,
• 2 showed strong culsterin in the minor
subset of cells
• Others: negative
EM(1)
• Were performed in selected case( 3 FDCTs
and 2 IDCTs)
• FDCT: long interwining process connected
by well-formed desmosome
• IDCT: complex interdigitating process
without intercellular junction, variable
number of lysosome and intermediate
filament
EM(2)
• Unclassifiable spindle tumor: nonspecific
features that lack membrane interdigitating
process, intercellular junction, dense bodies
and basal lamina
Clinical feature(1)
• Follow-up clinical information was
available in 9 FDCT(M: 58.4 m)
• 4 achieved apparent cure
• meta was noted in 5 cases
• None of the patient with FDCT is known to
have died
Clinical feature(2)
• IDCT occurred in older adult
• Four presented with solitary LN(+)
• Follow up clinical information was avaiable
in 5 IDCT cass
• Three achieved apparent cure
• Two presented with disseminated dx and
progressed rapidly to death from their dx
Clinicopathological Correlation
• No apparent correlation of behavior of
FDCT or IDCT with mitotic activity,
necrosis, degree of atypia or tumor location
• The two very aggressive IDCT had very
similar histiocyte-like morphology and
CD68(+) that was distinct from the other
three cases
Discussion(1)
• The distinction of FDCT from other
subtypes of dendritic cell tumor and other
spindle cell tumor requires a panel of IHC
stain(CD21, CD23, CD35, S-100, CD1a,
CD68, actin, desmin and CK)
• we demonstrate the additional marker,
clusterin, increases the diagnostic sensitivity
Discussion(2)
• Strong clusterin staining also distinguishes
FDCTs from other dendritic cell neoplasm
• Robust clusterin staining is useful as
supportive evidence for FDCT in cases with
weak or focal expression of the extablished
FDC markers
Discussion(3)
• CD21 is thought to be the most reliable
FDC marker with a sensitivity of 96%
• Weak and focal staining is a particular
problem in hepatosplenic FDCT cases with
an inflammatory pseudotumor-like
morphology
• Some have used CD21and CD35 cocktail or
additional marker(Ki-FDC1p, Ki-M4p, CAN.42, R4/23)
Discussion(4)
• In addition to be a supplemental marker,
clusterin staining can help classify FDCT
that is completely devoid of staining for
these traditional marker
• Strong clustrin expression shows specificity
for FDCTs among dendritic cell tumor
Discussion(5)
• IHC finding on 6 spindle cell tumor, NOS
suggest that clusterin may not be entirely
specific for FDCTs among all spindle cell
tumor
• The clinical finding in our cases supplement
previous report, behave as low gr sarcoma,
with tendency for local recurrence and late
metastases, some with castleman dx
Discussion(6)
• Attempt to correlate clinicopathologic
parameterw with clinical outcome have
been limited by the rarity of the tumor
• One previous study of 17FDCTs found a
statistically significant correlation between
intraabdominal location, significant
pleomorphism and a worse outcome
Discussion(7)
• IDCTs display a variable behavior from benign to
rapidly fatal dx
• No apparent association between mitoses, necrosis,
nuclear pleomorphism or extranodal location
• It’s interesting to speculate that IDCTs displaying
more histiocytic differentiation may be associated
with more aggressive behavior
Conclusion
• IHC for clussterin is of significant utility in
diagnostic evaluation of dendritic cell tumor
• Strong clusterin stain appears to be a highly
sensitive marker of FDCT
• Additional study is needed to delineate the
specificity of clusterin expression among a
broader spectrum of sarcoma and other
spindle cell tumor