Pediatric Oncologic Pathology
Moderators: Dr. Tony Bourne and Dr. Denis Benjamin
Case 3 -
Follicular dendritic cell sarcoma/tumour, low to intermediate
David Parham, MD
Chief of Pediatric Pathology
Arkansas Children's Hospital
Vice-Chair of Pathology
University of Arkansas for Medical Sciences
This 12 year-old Caucasian girl presented to her local pediatrician with swelling above her right
clavicle. Examination revealed a large, non-tender, freely movable soft tissue mass. CT scans revealed
a 2.8 x 3.0 x 5.0 cm, mass in the right supraclavicular region (Figure 1). There was an indistinct
margin of fat. The right clavicle showed no evidence of bone destruction. A 1.5 cm lymph node was also
noted in the right axilla, but no other lesions were found in the thorax or abdomen. Following an
incisional biopsy, an excision was performed, with removal of the right clavicle and en bloc resection.
Figure 1: Computed tomograph of upper thorax,
indicating a well-marginated, oval supraclavicular mass (arrow). There was no bony involvement.
Gross examination: The specimen consisted of a portion of bone with attached soft tissue and measured
6 x 3.5 x 3 cm. On sectioning, a soft to firm tan white soft tissue lesion measured 3 x 1.5 x 2 cm and
showed no gross bone invasion.
Microscopic examination: The lesion consisted of uniform, relatively bland, plump spindle cells
arrayed in fascicles and whorls. Some whorls resembled those of meningothelial meningioma and other
areas evoked burned out germinal centers. Focally abundant infiltrates of lymphocytes and plasma cells
were present. Abundant reticulin fibers surrounded tumor cells. Immunostains revealed uniform CD21
positivity, variable HLA-DR staining, and weak focal EMA positivity. Immunostains for pan-cytokeratin,
smooth muscle actin, S100, and vimentin were negative.
Case 3 - Slide 1
Ultrastructural examination: Micrographs revealed spindle cells with oblong nuclei and abundant,
marginated heterochromatin. The cytoplasm contained abundant dilated cisternae of rough endoplasmic
reticulum. Numerous intercellular junctions connected cytoplasmic processes and showed features of
rudimentary desmosomes, such as interconnecting filaments (Figure 2). A single structure resembling a
rudimentary lumen was noted in one micrograph. Admixed cells had features of histiocytes, such as
ruffled borders and lysosomes. Extracellular matrix consisted of collagen fibrils and amorphous
Figure 2: Electron micrograph showing tumor cells with spindly contours. Desmosomes connect
Follicular dendritic cell sarcoma/tumour, low to intermediate
Follow-up: Resection margins were close (less than 1 mm) but free of tumor. The patient received
external beam irradiation and chemotherapy with ifosfamide, carboplatin, and etoposide with no
significant side effects. Four years after completing her therapy, she showed no evidence of tumor in a
return clinic visit.
Differential diagnosis: Synovial sarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor,
leiomyosarcoma, rhabdomyosarcoma, fibromatosis, epithelioid sarcoma, interdigitating dendritic cell
sarcoma/tumour, fibroblastic reticular cell tumour, Langerhan cell histiocytosis, anaplastic large cell
Definition: Follicular dendritic cell sarcomas are low to intermediate grade neoplasms that
possess phenotypic features of the follicular dendritic cells found in the germinal centers of lymph
Because these lesions have variable grades and often show indeterminate clinical behavior,
the term "follicular dendritic cell tumour" is preferred by some. As a result, the WHO designates these
lesions as "follicular dendritic cell sarcoma/tumour" .
Classification of dendritic cell tumours: Dendritic cells are antigen-presenting cells found
in lymph nodes and skin and having features akin to histiocytes, particularly Langerhan cells. For this
reason dendritic cell tumours are typically included among histiocytic neoplasms such as Langerhan cell
histiocytosis and histiocytic sarcoma. This group also includes the similar but distinct neoplasms
interdigitating dendritic cell sarcoma/tumour and the recently described fibroblastic reticular cell
tumour . Dendritic cells share phenotypic features of antigen presenting cells but are distinguished
by their recipients. Follicular dendritic cells present antigens to B cell and interdigitating dendritic
cells present to T cells. As the name implies, they are also found in different regions of the lymph
node . As such, they are antigenically distinct, with interdigitating cells more closely resembling
Occurrence in children: Like "true" histiocytic sarcomas, dendritic cell tumours of all types
are vanishingly rare lesions that are typically the subject of case reports. Thus, tumours occurring in
children are generally not well recognized and may be mistaken for more common spindle cell neoplasms. A
recent report collected a series of four paediatric cases of interdigitating cell sarcoma and reviewed
the world literature on the subject . These cases arose in the left chest wall, vertebral body, lymph
nodes, and urinary bladder, respectively, suggesting a relatively high incidence of extranodal disease as
compared to adults. The authors found an additional four patients less than 20 years of age in their
literature search, which yielded a total of 33 other cases. Chan's series of 17 cases of follicular
dendritic cell tumours included two in older adolescents, one arising in the tonsils and the other in the
soft tissue of the neck . No paediatric cases were included among a slightly smaller series from
Memorial Sloan-Kettering Cancer Center . The rarity of the latter lesions suggests that they are
under-reported, possibly due to lack of readily available immunohistochemical reagents necessary for
their diagnosis. On the other hand, three adolescents are included among the initial series of 11
fibroblastic reticulum cell tumours . Nonaka, Birbe, and Rosai have suggested that the inflammatory
myofibroblastic tumour represents a proliferative lesion of fibroblastic reticulum cells . This
view is not widely accepted, but it illustrates the possibilities these cell types offer when defining
poorly understood spindle cell lesions.
Defining features: Follicular dendritic cell sarcomas appear as low grade spindle cell lesions
with a characteristic whorled pattern reminiscent of meningioma. The constituent cells vary from
elongate to ovoid in profile, and their cytoplasm possesses a lightly eosinophilic hue. Generally the
nuclei appear low grade, with finely dispersed chromatin and a small central nucleolus, and as in
meningioma pseudonuclear inclusions may be seen. Worrisome features include a high cellularity, nuclear
atypia, and significant mitotic activity with atypical figures (although 1-10 per 10 hpf is the rule).
Uninvolved lymphoid tissue is usually present, so that germinal centers may be seen. Cases occurring in
the liver and spleen have histologic features highly resembling inflammatory myofibroblastic tumour and
have been associated with EBV infection .
Confirmation of the diagnosis requires ultrastructural examination and/or immunohistochemistry.
Follicular dendritic cell tumours have a distinctive ultrastructural appearance, with elongate, slender,
cytoplasmic processes connected by desmosomes. In contradistinction to other histiocytic tumours,
Birbeck granules or numerous lysosomes are not seen .
Immunohistochemical findings in follicular dendritic cell tumours are also distinctive, but the stains
required are not widely available. Happily, they can usually be performed by reference laboratories.
The primary finding is positivity for markers of complement receptors, such as CD21 and CD35, and the Fc
receptor CD23. Of note is that the latter marker is also the EBV receptor in B cells, explaining the
susceptibility of these cells to EBV infections. Positivity for one or a combination of these markers
may be present. However, they are not absolutely specific and may be found in other haematopoietic
cells, particularly B cells, but in the context of spindle cell lesions they are reliable. When
performing immunostaining for these antigens, a good epitope retrieval method is critical, and CD35
appears to be the most consistent marker . The combination of desmosomes and positivity for these
markers is diagnostic.
New data suggests that clusterin expression may be used in lieu of the CD markers , but to date
its immunostain is not available in reference laboratories. EMA and/or cytokeratin may also be positive
. Unlike the present case, vimentin in usually (but not always) positive, and not unexpectedly,
and desmoplakin  can also be positive. CD20, CD45 and actin positivity may also be
These tumours are variably positive for S100 and CD68, as opposed to the uniform reactivity of
interdigitating follicular cell tumours for the former marker and histiocytic sarcoma for the latter.
Interdigitating follicular cell tumours do not stain with complement receptor markers . Negativity
for CD1a serves to distinguish follicular dendritic cell tumours from Langerhan cell histiocytosis .
Distinction from other lesions: The cardinal rule to observe for diagnosis of these lesions
is to remember that they are rarer than hens' teeth, particularly in children, so that a careful work-up
is in order. Also they span features of epithelial, hematopoietic, and mesenchymal tumours, so the
differential diagnosis includes a number of diverse entities. Involvement of lymphoid organs is typical,
but extranodal sites may be involved . Some lesions may be associated with Castleman's disease, so
the clinical setting can be helpful. In the present case, the surgeon's original assumption that the
involved tissue was a supraclavicular lymph node proved correct, in spite of considerations by other
specialists that this was a soft tissue lesion.
Important considerations for differential diagnosis include soft tissue tumours with epithelial
differentiation, such as synovial sarcoma and epithelioid sarcoma. These should be negative for lymphoid
markers, and molecular studies may be helpful in confusing cases. The features listed above, especially
complement receptor expression and processes with desmosomes, should separate follicular dendritic cell
tumours from other hematopoietic neoplasms.
Clinical outcome: Generally follicular dendritic cell tumours have a good outcome, similar to
the present case. As such their behavior more closely parallels a low grade soft tissue tumour than a
hematopoietic malignancy. Local recurrences occur in about one-third of cases, and distant metastases in
about one-sixths. About five per cent of patients have died of their disease . Recurrent lesions may
show cytohistologic evidence of tumour progression .
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- Weiss LM, Grogan TM, Muller-Hermelink HK, Stein H. Follicular dendritic cell sarcoma/tumour. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours, Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001;286-288.
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