Synchronous interdigitating dendritic cell sarcoma and B-cell small lymphocytic lymphoma in a lymph node

Article (PDF Available)inArchives of pathology & laboratory medicine 130(4):544-7 · May 2006with29 Reads
DOI: 10.1043/1543-2165(2006)130[544:SIDCSA]2.0.CO;2 · Source: PubMed
A gradually enlarging axillary mass in a 79-year-old man was excised. The specimen was processed for light microscopy, immunohistochemical studies, and electron microscopy; gene rearrangement studies were also performed. A diagnosis of an interdigitating dendritic cell tumor of the lymph node and a B-cell small lymphocytic lymphoma occurring in the same anatomic location was made. We found that although rare cases of interdigitating dendritic cell tumor with an associated secondary malignancy have been described in the literature, to our knowledge, this is the first report of interdigitating dendritic cell tumor and synchronous neoplasm diagnosed at the same site. A possible relationship between the 2 disorders is also discussed.


544 Arch Pathol Lab Med—Vol 130, April 2006 Synchronous Lymph Node Sarcoma and Lymphoma—Cossu et al
Synchronous Interdigitating Dendritic Cell Sarcoma and
B-Cell Small Lymphocytic Lymphoma in a Lymph Node
Antonio Cossu, MD; Angelo Deiana, MD; Amelia Lissia, MD; Maria Filomena Dedola, MD; Lucia Cocco, MD;
Giuseppe Palmieri, MD; Francesco Tanda, MD
A gradually enlarging axillary mass in a 79-year-old man
was excised. The specimen was processed for light micros-
copy, immunohistochemical studies, and electron micros-
copy; gene rearrangement studies were also performed. A
diagnosis of an interdigitating dendritic cell tumor of the
lymph node and a B-cell small lymphocytic lymphoma oc-
curring in the same anatomic location was made. We
found that although rare cases of interdigitating dendritic
cell tumor with an associated secondary malignancy have
been described in the literature, to our knowledge, this is
the first report of interdigitating dendritic cell tumor and
synchronous neoplasm diagnosed at the same site. A pos-
sible relationship between the 2 disorders is also discussed.
(Arch Pathol Lab Med. 2006;130:544–547)
endritic cells (DCs) constitute a complex system,
made up of several distinct cell populations occu-
pying discrete portions of lymphoid and nonlymphoid or-
gans that are interconnected by defined pathways of
movement. In each site, the DCs share morphologic, im-
munophenotypic, and functional characteristics, the most
notable being the ability to capture antigens in an im-
munogenic form in situ and initiate B-cell– and T-cell–
mediated immunity.
The DC compartment comprises several subtypes: fol-
licular DC of the germinal center of lymph node; Langer-
hans cell (LC) of the skin; interstitial DC, representing the
counterpart of LC in parenchymal organs; indeterminate
cell (veiled cell), derived from LC or interstitial DC and
migrating into local lymphoid tissue after antigen capture;
and interdigitating DC (IDC) of the T-zone of the lymph
node. Follicular DCs are characterized by the presence of
desmosomes and the expression of the following pheno-
type: CD21
, CD35
, CD1a
, and S100 protein positive
or negative. Characteristically, LCs and interstitial DCs
show intracytoplasmic Birbeck granules ultrastructurally
and display the following immunohistochemical profile:
Accepted for publication December 16, 2005.
From the Institutes of Anatomic Pathology and Histopathology (Drs
Cossu, Deiana, Lissia, Cocco, and Tanda), and Radiology, Radiotherapy
section (Dr Dedola), University of Sassari, and C.N.R., Istituto di Chim-
ica Biomolecolare (Dr Palmieri), Sassari, Italy.
The authors have no relevant financial interest in the products or
companies described in this article.
Reprints: Antonio Cossu MD, Institute of Anatomic Pathology and
Histopathology, via Matteotti 58, 07100 Sassari, Italy (e-mail: cossu@
, S100 protein positive, CD21
, CD35
, and CD86
Indeterminate cells display the same immunophenotype
as LCs, but do not have Birbeck granules.
The IDCs are present within lymph nodes, tonsils, the
spleen, and other lymphoid tissue. They resemble LCs
morphologically, except for the absence of intracytoplas-
mic Birbeck granules. They are S100 protein positive,
, and rev eal complex interdigitating cellular junc-
tions ultrastructurally. The IDCs are characteristically lo-
cated in T-cell domains, that is, the paracortex and inter-
follicular areas of lymph nodes and tonsils, and the peri-
arteriolar lymphoid sheath of the spleen. They are typi-
cally surrounded by helper T cells.
Tumors derived from DCs share morphologic, imm u-
nohistochemical, and microscopic features similar to the
nonneoplastic counterparts; they are extremely rare, rep-
resenting less than 1% of neoplasms present in the lymph
Among tumors arising from the DCs system, to our
knowledge, only a few cases (39 cases) of IDC sarcoma/
tumor (IDCT) have been reported in the literature; on an-
alyzing their main clinical pathologic data, occurrence of
a secondary solid or hematologic neoplasm was seen in 7
We report an IDCT that was found in a lymph node
biopsy that also showed a synchronous B-cell small lym-
phocytic lymphoma.
To our knowledge, this report seems to be the first case
of IDCT and B-cell small lymphocytic lymphoma simul-
taneously diagnosed, and our review of the literature
seems to suggest that the association of IDCT and malig-
nant secondary neoplasm, par ticularly B-cell small lym-
phoproliferativ e disorders, is more than coincidental.
A 79-year-old man who had severe dilated cardiomyopathy
was admitted into a local clinic with a history of inguinal hernia
and painless, gradually enlarging axillary lymphadenopathy.
On admission, he did not present systemic symptoms, and re-
sults from laboratory tests were within the normal limits. A com-
plete blood count revealed a hemoglobin level of 10.2 g/dL, a
platelet count of 280.2 10
cells/L, and a white blood cell
count of 9800 cells/L. Peripheral blood smear was reported as
normal. Physical examination and radiographic examination, in-
cluding a total body computed tomography scan, showed no oth-
er lesions elsewhere.
Manual reduction of the hernia was successfully performed. At
the same time, the axillary lymph nodes were excised, and the
specimen consisted of a solid, firm, whitish gray, capsulated mass
Arch Pathol Lab Med—Vol 130, April 2006 Synchronous Lymph Node Sarcoma and Lymphoma—Cossu et al 545
Figure 1. Microscopic features of interdigitating dendritic cell sarcoma/tumor (IDCT) of the lymph node: proliferation of atypical spindle cells
with irregular nuclei and abundant cytoplasm. Numerous mitotic figures are also visible (hematoxylin-eosin, original magnification
Figure 2. Immunohistochemistry for S100 protein shows immunoreactivity of the proliferating spindle cells in IDCT (original magnification
Figure 3. Ultrastructure of IDCT. The spindle cells show a deeply indented irregular nucleus and scattered intracytoplasmic organelles. Birbeck
granules and desmosomes are not appreciable (original magnification
Figure 4. B-cell small lymphocytic lymphoma shows a mixture of atypical lymphoid cells and larger nucleolated cells (hematoxylin-eosin, original
Figure 5. IDCT and B-cell small lymphocytic lymphoma. Positive immunoreactivity for CD20 in lymphoma cells (original magnification
Figure 6. Polymerase chain reaction testing for immunoglobulin (Ig) H gene rearrangement showing clonal IgH rearrangement. Lanes: A, molec-
ular weight marker; B, positive control from a patient with B cell lymphoma (frozen tissue); C, reactive lymph node, as a negative control; and
D, the present case.
546 Arch Pathol Lab Med—Vol 130, April 2006 Synchronous Lymph Node Sarcoma and Lymphoma—Cossu et al
Summary of Interdigitating Dendritic Cell Sarcoma/Tumors (IDCTs) Associated With Secondary Malignancy
Source, y Age, y/Sex Site Associations Interval
Hammar et al,
1991 67/M Cervical lymph node B follicular center cell lym-
13 y before IDCT
Horschowski et al,
8/M Lymph nodes, colomesen-
teric masses
T lymphoblastic lymphoma 5 mo before IDCT
Nakamura et al,
70/M Submandibular lymph node Adenocarcinoma of the
stomach and hepatocellu-
lar carcinoma of the liver
4 y after IDCT
55/F Cervical lymph node Carcinoma of the breast 13 y before IDCT
Vasef et al,
1995 56/F Cervical and axillary lymph
B-cell small lymphocytic
9 mo before IDCT
Gaertner et al,
2001 70/M Axillary lymph node Carcinoma of the colon 6 y before IDCT
77/F Tonsil B-cell small lymphocytic
1 y before IDCT
Present case 79/M Axillary lymph node B-cell small lymphocytic
(4.5 cm in diameter). The specimen was processed for light mi-
croscopy and electron microscopy.
Microscopically, most of the lymph node was replaced by a
spindle-cell proliferation intermingled with mature lymphocytes
and few plasma cells. The neoplastic cells formed loosely com-
pact bundles arranged in a storiform pattern, showed abundant
eosinophilic cytoplasm, and had round-to-ovoid, vesicular nuclei,
often with deeply cleav ed, irregular nuclear membranes (Figure
1). Nucleoli were generally prominent. The spindle cells were
large, exceedingly atypical, and frequently multinucleated. Mi-
totic activity, including atypical mitoses, was high (mean 4–5
10 high-power fields), and focally heavy collagen deposition
was observed, with some neoplastic cells encased within dense
fibrous tissue. Immunohistochemistry performed on paraffin-em-
bedded tissue showed the neoplastic cells to be immunoreactive
for S100 protein (Figure 2), vimentin, HLA-DR,
trypsin, and weakly immunoreactive for actin and CD34; nega-
tive for HMB-45, cytokeratins (AE1/AE3), CD1a, CD45 (LCA),
CD20 (L26), CD45RO (UCHL-1), CD21, CD35, CD68, CD30, ep-
ithelial membrane antigen, and desmin. Ultrastructurally (Figure
3), the tumor cells showed oval to irregularly shaped nuclei with
deep indentations. The chromatin was finely granular and one or
more large nucleoli were seen. The cytoplasm was abundant,
with numerous mitochondria and scattered lysosomes.
Neoplastic cells showed elongated interdigitating cytoplasmic
processes and absence of desmosomes, melanosomes, or Birbeck
A portion of this lymph node and 2 adjacent lymph nodes of
2 1 cm each sho w ed replacement of the architecture by a pre-
dominantly small-cell population intermingled with smaller
numbers of larger nucleolated cells (Figure 4). The small cells
seemed to have a striking subsinusal pattern of distribution, and
had little cytoplasm and small, somewhat irregular nuclei. Scat-
tered mitoses were observed. This proliferation was made up of
lymphoid cells with the B phenotype (CD45
and CD20
; Figure
5) and was associated with a minor component of small CD3
T cells. The vast majority of proliferating cells ex-
pressed CD5 and CD23; CD10 and nuclear cyclin D1 were neg-
ative. A meshwork of CD23
follicular DCs was focally present
among the atypical lymphoid cells. A clonal immunoglobulin (Ig)
heavy chain gene rearrangement was detected by means of a
polymerase chain reaction assay of deoxyribonucleic acid extract-
ed and amplified from the formalin-fixed, paraffin-embedded
lymphoid tissue (Figure 6).
The final diagnosis was IDCT associated with B-cell small lym-
phocytic lymphoma. The patient refused postoperative hospital-
ization and further clinical investigations and treatment. Subse-
quently, his condition worsened because of progressive dilated
cardiomyopathy, and 2 months after surgery he died from heart
failure. Postmortem examination was not performed.
This report, based on morphologic and immunopheno-
typic features, describes a rare case of IDCT associated
with a synchronous B-cell small lymphocytic lymphoma.
The IDCT is a neoplastic proliferation of spindle-to-oval–
shaped cells with phenotypic features similar to those of
IDCs found in normal tissues. The designation sarcoma/
tumor in the literature is used because of the variable cy-
tologic grade and clinical behavior encountered in these
This malignancy is very uncommon and only 39 cases
have previously been documented in the literature, to our
knowledge. IDCT usually occurs in adults (age range, 2–
86 years), with a slight male predominance (male-female
ratio, 1.16). Most IDCTs are found in the lymph nodes.
Rare cases of this neoplasm occur in extranodal lymphoid
tissue, such as tonsil, nasopharynx, skin, intestine, testis,
spleen, bladder, and salivary gland. Approximately half of
the patients die of the disease within an average period
of 6 to 7 months (range, 1 week–16 months). The response
to therapy is also generally poor, although some patients
experience either long disease-free survival or complete
One very interesting fact regarding this tumor, although
not surprising, is the existence of a concomitant tumor in
the clinical history of some patients. Such an association
has been well documented for DC-related disorders, and,
in our review, we found that a diagnosis of a malignant
secondary neoplasm that may follow or precede IDCT was
reported in 7 patients
(Table). Four of the 7 cases de-
scribed are malignant hematologic tumors, consistent
with a non-Hodgkin lymphoma (NHL), either of a T-cell
line (1 case)
or a small B-cell type (3 cases).
the number of these cases is low, the occurrence (17%) is
greater than expected.
Our case also represents an IDCT synchronous to B-cell
small lymphocytic lymphoma in the same lymph node; to
our knowledge, such an occurrence simultaneously diag-
nosed in the same biopsy has not previously been report-
ed. Indeed, the high freq uency of association with NHL
(12% including the present case and the previous reports)
suggests a clear relationship and raises interesting ques-
tions concerning the pathogenesis of a secondary malig-
nancy (particularly, a small B-cell lymphoproliferative dis-
order) in IDCT.
Arch Pathol Lab Med—Vol 130, April 2006 Synchronous Lymph Node Sarcoma and Lymphoma—Cossu et al 547
It is generally accepted that escape f rom immune sur-
veillance is a fundamental feature of tumors that contrib-
utes to their uncontrolled growth.
cells are one of the most efficient vehicles for the delivery
of tumor antigens; dysfunction of DCs, showing a mor-
phologically and phenotypically immature population
with a reduced response against neoplastic cells, has al-
ready been reported in different malignancies, including
hepatocellular carcinoma
and chronic lymphocytic leu-
In IDCT, a specific defect of transformed neoplastic DCs
in immune surveillance could also contribute to the onset
or dev elopment of concurrent malignant tumors. Interest-
ingly, IgD
naı¨ve B cells in T-cell areas of the human mes-
enteric lymph nodes attach directly to IDCs by 1 or 2 cy-
toplasmic projections, and a small number of IDCs are
present in B-cell–rich areas, such as the periphery of the
mantle zones or primary follicles.
The functional role of
these IDCs in B-cell–rich areas remains unclear, but these
data suggest that IDCs are more deeply in v olved in the
B-cell–mediated immunologic responses than was previ-
ously thought, and that DCs may directly modulate dif-
ferentiation and proliferation of small B-cell lymphocytes.
Clearly, much remains to be investigated beyond these
tentative studies to define the molecular mechanism in-
volved in the interactions between DC and B cells and
their possible role in human diseases involving B cells,
such as lymphomas. Some a uthors hav e postulated that
therapeutic agents in a patient with NHL play a role in
the dev elopment of DC neoplasms,
but this hypothesis
has not been confirmed and, in our case, the patient had
not previously been treated and IDCT was found with a
B-cell small cell lymphoma.
In conclusion, our review confirms that IDCT is both a
well-defined and extremely rare entity; moreover, the
more than coincidental association with other NHLs is of
great interest, and our report of an IDCT occurring in the
same lymph node simultaneously with a B-cell small lym-
phocytic lymphoma further supports such an association.
However, additional studies should be performed to clar-
ify the exact relationship between IDCT and small B-cell
NHL and the possible pathogenetic factors.
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    • "Several findings support the notion that LCH is a clonal proliferation of phenotypically immature Langerhans cells including familial occurrence in twins in very rare cases. A broad range of histiocytic disorders have been noted to have evidence of transdifferentiation101112131415161718192021. These include examples of histiocytic neoplasms with clonal immunoglobulin heavy-chain gene rearrangements that are identical to those seen in synchronous or metachronous B-cell lymphomas. "
    [Show abstract] [Hide abstract] ABSTRACT: Histiocytic disorders have been noted to have evidence of transdifferentiation; examples of cases with combinations of different lineages have been shown. In our index case, we identified interdigitating dendritic cell (IDC) differentiation in a case of Langerhans cell histiocytosis (LCH). Little is currently known about the genetics of IDC sarcoma (IDCS) because they are exceedingly rare. Using array comparative genomic hybridization (aCGH), we evaluated 4 cases of IDCS and compared them with our index case, as well as genetic abnormalities previously found in LCH. Four cases of paraffin-embedded samples of IDCS and 1 case of LCH with IDC differentiation were evaluated using aCGH. Array CGH results showed no abnormalities in a case of LCH with interdigitating cell differentiation. In 3 of 4 cases of IDCS, genetic abnormalities were identified; 1 case had no identifiable abnormalities. Interdigitating dendritic cell sarcoma case 1 had gains of 3q and 13q; IDCS case 2 had trisomy 12; IDCS case 3 had deletions of 7p, 12p, 16p, 18q, 19q, and 22q; and IDCS case 4 had no detectable abnormalities. Our index case, LCH with IDC differentiation, showed no abnormalities by aCGH. A number of LCH cases do not have detectable genetic abnormalities. In contrast, 3 of 4 cases of IDCS evaluated had identifiable abnormalities by aCGH. Furthermore, 2 of these shared abnormalities, albeit of large genetic regions, with published abnormalities seen in LCH. No recurrent abnormalities were identified in the IDCS cases. However, the possibility of a relationship between IDCS and LCH cannot be entirely excluded by these results.
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    • "However, recent studies have shown that histiocytic/dendritic cell sarcomas and some lymphoproliferative diseases, such as follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and hairy cell leukemia, may occur in the same individual and interestingly, these neoplasms are clonally related. This phenomenon is dubbed “transdifferentiation”.[12345678] There have been several reports showing synchronous IDCS and CLL/SLL; however, only one case of concurrent LCS and CLL/SLL has been documented in the English literature.[9] "
    [Show abstract] [Hide abstract] ABSTRACT: the phenomenon that histiocytic/dendritic cell sarcomas may be transformed from lymphoproliferative diseases is dubbed 'transdifferentiation'. Langerhans cell sarcoma (LCS) transdifferentiated from chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) is extremely rare. The underlying mechanisms of LCS tumorogenesis and its transdifferentiation from CLL/SLL are largely unknown. the authors strive to further characterize LCS, to understand the potential molecular changes in LCS and the underlying mechanisms of CLL/SLL transformation to LCS. a progressively enlarging right inguinal lymph node from a 68-year-old female patient with a history of CLL was biopsied and submitted for flow cytometry analysis, routine hematoxylin, and eosin (H and E) stain and immunohistochemical study. Furthermore, clonality study (fluorescent in situ hybridization (FISH) analysis with a CLL panel probes) and BRAF V600E mutation study (pyrosequencing and immunostain) were performed. two different neoplasms, LCS and CLL/SLL, were discovered to occur simultaneously in the same lymph node. These two entities were shown to be clonally related. More importantly, for the first time, BRAF V600E mutation was detected in LCS. LCS can be transdifferentiated from CLL/SLL and BRAF V600E mutation may provide the foundation for alternative therapy of LCS.
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