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Symposium
Cytology of soft tissue tumors: Benign soft tissue tumors
including reactive, nonneoplastic lesions
Introduction
Soft tissues are the supportive tissue of various organs as
well as the nonepithelial, extraskeletal structures. They
include adipose tissue, fibrous connective tissue, skeletal
muscle, blood vessels, and the peripheral nervous system.
Soft tissues are almost entirely derived from the mesoderm
except for the peripheral nerves. Soft tissue tumors, being
a large heterogeneous group of neoplasms, are classified
according to histogenesis, as detailed below.[1] Most have
benign and malignant counterparts; some are of borderline
malignant potential with aggressive local invasion.
The incidence of benign soft tissue tumors is about ten times
that of malignant ones. Benign deep masses in adults are
usually due to intramuscular lipoma. Extremity masses larger
than 5–7 cm and deeper than subcutaneous tissue, favour the
diagnosis of a malignant soft tissue tumor. Benign tumors are
usually superficial and well defined or encapsulated masses
showing slow growth. [1] Of the imaging methods commonly
used for evaluation, magnetic resonance imaging best defines
the relationship between a tumor and its adjacent anatomic
structures, such as compartment boundaries, nerves,
vessels, and muscle.[2] This article will discuss the fine needle
aspiration cytology (FNAC) of benign soft tissue tumors,
including reactive and nonneoplastic lesions. The complete
list of such tumors is given in Table 1 for ready reference,
followed by the FNAC features in detail.
WHO (2002) Classification of Soft Tissue Tumors
Soft tissue tumors are divided into the following four
categories:
Benign: These usually do not recur locally, and if they
do, the recurrence is nondestructive and almost always
readily curable by complete local excision. Morphologically
benign lesions which are extremely rare, may give rise to
distant metastases that cannot be predicted on the basis of
VENKATESWARAN K IYER
Department of Pathology, AIIMS, New Delhi, India
For correspondence: Dr. Venkateswaran K Iyer, Department of Pathology, AIIMS, New Delhi, India. E-mail: iyer_venkat2@rediffmail.com
Journal of Cytology / July 2008 / Volume 25 / Issue 3
routine, histological evaluation. Cutaneous benign fibrous
histiocytoma is the best example.
Intermediate (locally aggressive): These tumors show an
infiltrative and locally destructive growth pattern; however,
they do not metastasise. The example in this category is
fibromatosis.
Intermediate (rarely metastasising): These tumors are
often locally aggressive but in some cases, they also have a
tendency to produce distant metastases (usually in a lymph
node or lung). This risk is low (< 2%). The classic examples
are plexiform fibrohistiocytic tumors and angiomatoid fibrous
histiocytoma.
Malignant: Soft tissue sarcomas are locally destructive
with the potential to recur; the risk of distant metastasis is
significant. (Depending on the histological type and grade,
the potential ranges from 20 to almost 100%.)
Fine Needle Aspiration Cytology
Benign soft tissue tumors usually present with superficial small
swellings, usually in the subcutaneous tissue, and are best
assessed by FNAC.[3-6] Although numerous histopathological
entities are currently known (as listed above), the majority are
rare and can only be diagnosed on histology. The commonly
encountered soft tissue tumors and lesions and their FNAC
appearance are described below.
Lipoma
This is the most commonly encountered swelling that
is subjected to FNAC. Clinical findings of the swelling
are essential in its differentiation from subcutaneous
fibroadipose tissue, accurate needle placement within the
mass being the most important criterion. Lipomas are usually
solitary but may be multiple, and the swelling slips under
the examining hand.
Aspirates show adipose tissue which is indistinguishable
from normal fibroadipose tissue [Figure 1]. Delicate vessels
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Iyer: Cytology of benign soft tissue tumors

Table 1: The tumors under the benign category Cavernous

Arteriovenous
Adipocytic tumors
Venous
Benign
Intramuscular
Lipoma
Synovial
Lipomatosis
Epithelioid hemangioma
Lipomatosis of nerve
Angiomatosis
Lipoblastoma/lipoblastomatosis
Lymphangioma
Angiolipoma
Chondro-osseous tumors
Myolipoma
Benign
Chondroid lipoma
Soft tissue chondroma
Extrarenal angiomyolipoma
Tumors of uncertain differentiation
Extra-adrenal myelolipoma
Benign
Spindle cell/pleomorphic lipoma
Intramuscular myxoma—Including cellular variant
Hibernoma
Juxta-articular myxoma
Fibroblastic/myofibroblastic tumors
Deep (“aggressive”) angiomyxoma
Benign
Pleomorphic hyalinizing angiectatic tumor
Nodular fasciitis
Ectopic hamartomatous thymoma
Proliferative fasciitis
Proliferative myositis
Myositis ossificans
Fibro-osseous pseudotumor of the digits
Ischemic fasciitis without much fibrous tissue are the rule.[7,8] The fat cells
Elastofibroma are univacuolated with nuclei pushed to the periphery.
Fibrous hamartoma of infancy Intramuscular lipomas may be admixed with skeletal muscle.
Myofibroma/myofibromatosis
Fibromatosis colli These have to be differentiated from myxomas which also occur
Juvenile hyaline fibromatosis in this location, the aspirates of which have myxoid material
Inclusion body fibromatosis with stellate cells.[9] The presence of atypical nuclei may be
Fibroma of tendon sheath
Desmoplastic fibroblastoma indicative of benign lesions such as atypical lipoma or a well
Mammary-type myofibroblastoma differentiated liposarcoma. Lipoblasts in the aspirate usually
Calcifying aponeurotic fibroma
indicate a well differentiated liposarcoma. However, lipid-
Angiomyofibroblastoma
Cellular angiofibroma laden macrophages may mimic lipoblasts making cytological
Nuchal-type fibroma identification difficult. The presence of these findings
Gardner fibroma
Calcifying fibrous tumor
indicates the necessity for histological examination for proper
Giant cell angiofibroma evaluation, which can be recommended on FNAC.
Intermediate (locally aggressive)
Superficial fibromatoses—Palmar/plantar
Desmoid-type fibromatoses Benign Nerve Sheath Tumor
Lipofibromatosis
So-called fibrohistiocytic tumors Schwannomas and neurofibromas may be solitary or multiple
Benign
Giant cell tumor of tendon sheath (in neurofibromatosis) and are commonly aspirated for
Diffuse-type giant cell tumor diagnosis. Aspiration from neurofibromas is usually painful.
Deep benign fibrous histiocytoma Aspirates are cellular and show spindle cell morphology with
Intermediate (rarely metastasizing)
Plexiform fibrohistiocytic tumor moderate cellularity. A fibrillary background is common in
Giant cell tumor of soft tissues both schwannomas and neurofibromas.[10] Nuclei of both
Smooth muscle tumors
tumors are long with pointed ends and have a “buckled”
Angioleiomyoma
Deep leiomyoma or twisted appearance [Figure 2]. The presence of nuclear
Genital leiomyoma palisading (or Verrocay bodies) favors a schwannoma over
Leiomyosarcoma—Excluding skin
Pericytic (perivascular) tumors
a neurofibroma but FNAC cannot help make this distinction
Glomus tumor (and variants) cannot be reliably made in its absence.
Malignant glomus tumor
Myopericytoma
Skeletal muscle tumors
S o m e a s p i r a t e s s h o w n u c l e a r e n l a rg e m e n t a n d
Benign pleomorphism.[11] This is a common finding in large benign
Rhabdomyoma nerve sheath tumors that warrants a careful search for mitotic
Adult
Fetal figures and histological examination of an excision biopsy
Genital type is essential for proper evaluation. The presence of mitotic
Vascular tumors figures even in aspirates not showing nuclear pleomorphism,
Benign
Hemangiomas of subcutaneous and deep soft tissue may indicate transformation to a malignant peripheral nerve
Capillary sheath tumor.

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Iyer: Cytology of benign soft tissue tumors

Fibromatosis histological examination is needed for diagnosis.

This is a locally aggressive tumor and is currently classified
in the intermediate WHO grade. However, this is a common
tumor which is frequently assessed by FNAC. It has site
predilections which should be taken into account before the
interpretation of the FNAC findings.
Aspirates from fibromatosis have variable cellularity.[12,13]
Those with low cellularity are benign in appearance [Figure 3]
and are composed of spindle-shaped fibroblasts arranged in
groups interspersed with collagen (and not fibrillary material
as with nerve sheath tumors). Single cells are seen in the
background; mitotic figures are rare.
Aspirates from aggressive fibromatosis are more cellular
although mitoses are rare to absent.[12] Collagen matrix is more
difficult to identify in aspirates [Figure 4]. Such tumors are
difficult to differentiate from low-grade spindle cell sarcomas
and hence, an inconclusive report on cytology and a subsequent
Leiomyoma
Leiomyomas are much less common in the subcutaneous
region as compared to lipomas, nerve sheath tumors,
and fibromatosis. Leiomyoma is differentiated from
leiomyosarcoma based on the mitotic counts done as part
of the histological examination. As such, FNAC has a limited
role in diagnosis. The main objective is the identification of
smooth muscle differentiation on FNAC which may be difficult
to accomplish. A diagnosis of a nonspecific, benign spindle
cell tumor is usually returned.
Aspirates from leiomyoma are usually sparsely cellular,
although some aspirates may be cellular.[14] The tumor cells
may have clear-cut, spindle-shaped cytoplasmic processes on
either side that stain pale blue in Giemsa stain [Figure 5]. Bare
nuclei may predominate in some aspirates and if necrosis is
found, a differential diagnosis with a leiomyosarcoma would

Figure 1: Aspirate from lipoma showing normal looking adipose tissue with Figure 2: Aspirate from benign nerve sheath tumor showing Þbrillary back-
many capillary sized blood vessels (MGG, x200) ground and sparse cellularity of spindle cells (Pap, x200)

Figure 3: Aspirate from Þbromatosis showing sparse cellularity and col- Figure 4: Aspirate from aggressive Þbromatosis showing cellular spindle
lagenous stroma (Pap, x400) cell lesion without collagen (Pap, x400)

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Iyer: Cytology of benign soft tissue tumors
require a biopsy.
Benign fibrous histiocytoma group
This is a group of neoplasms which on aspiration, show an
admixture of spindle-shaped fibroblastic cells and polygonal
histiocytic cells. A number of tumors such as dermatofibroma,
tendon sheath fibroma, and proliferative fasciitis among
others, have a similar appearance on aspiration, and hence,
a definite diagnosis of benign fibrous histiocytoma cannot
be made.[15]
Aspirates from benign fibrous histiocytomas show spindle-
shaped fibroblasts with collagenised stroma and polygonal
cells with a moderate amount of foamy cytoplasm [Figure
6]. Giant cells may be seen including Touton giant cells.
May-Grünwald-Giemsa (MGG) staining may show polygonal
cells with blue cytoplasm; mitotic figures are absent.
Pleomorphism may be seen in the giant cells.
Giant cell tumor of the tendon sheath
This tumor usually occurs in the fingers and toes and may
be associated with trauma. It is still uncertain whether it
represents a true neoplasm or a reactive proliferation in
response to trauma. It is mostly considered to belong to the
benign fibrous histiocytoma group. However, as its typical
clinical and cytological features permit diagnosis, it requires
separate mention. Location is classical and radiological
demonstration of the lack of bone involvement is useful in
diagnosis.
Aspirates show multinucleated giant cells of osteoclastic
cell type and two kinds of stromal cells: spindle-shaped cells
and polygonal cells with cytoplasm.[16] Nuclear grooves are
frequent in the stromal cells [Figure 7]; binucleated cells are
seen.
Unlike the giant cell tumor of the bone which may involve
soft tissues, the cellularity of the aspirates is less in giant
cell tumors of the tendon sheath. The latter also show less
pleomorphism of the stromal component and show the
presence of typical polygonal and binucleate cells.
Benign tumor-like and reactive conditions of soft tissues
A number of conditions with unclear etiology are grouped
together under the general category of tumor-like conditions
of the soft tissue. It is now clear that a majority of these
are actually neoplastic and hence, the term, “tumor-like” is
inappropriate. Although these are grouped under neoplasms
in the WHO classification, they are still regarded by tradition
as being tumor-like or reactive conditions. Of these, the
most important are nodular fasciitis, proliferative fasciitis,
proliferative myositis, myositis ossificans, and inflammatory
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pseudotumor. Fine needle aspiration cytology of these entities
is considered below, along with atypical fibroxanthoma which
is a benign tumor with features mimicking malignancy.
Inflammatory pseudotumor
Alhough this tumor shows cytogenetic and molecular
abnormalities which place it within the neoplastic category,
it is still best regarded as a morphologic entity showing
mainly inflammatory cells with a pleomorphic spindle cell
component mimicking a tumor. The term, “pseudotumor”
is therefore, appropriate. As the atypical spindle cells
are myofibroblastic, it can be termed as an inflammatory
myofibroblastic tumor. It can occur in any location and in
different age groups including children, presenting as a mass
lesion that is commonly subjected to FNAC.
Aspirates from inflammatory pseudotumors usually have an
inflammatory background with a predominance of acute or
chronic inflammatory cells in different cases; plasma cells are
frequent. However, the most striking feature is the presence
of pleomorphic spindle cells and these aspirates are usually
suspected to be malignant [Figure 8]. An inflammatory
malignant fibrous histiocytoma is a close differential that
usually has tumor giant cells which are not an important
feature of inflammatory pseudotumors. It is therefore,
important not to diagnose a malignancy in these cases,
but to instead produce an inconclusive report stating the
necessity for a biopsy characterization.[17] On Giemsa-stained
slides, the myofibroblastic cells have characteristic grayish
blue cytoplasm.
Atypical fibroxanthoma
This is another tumor which can be misdiagnosed as being
malignant on aspiration. This tumor typically occurs as a small
skin nodule on the sun-exposed skin of elderly individuals. On
aspiration, highly pleomorphic cells are seen and a myxoid
background may be present [Figure 9]. It is important not to
misdiagnose this as a malignancy but to give an inconclusive
report asking for a biopsy diagnosis.
Nodular fasciitis, proliferative fasciitis, and proliferative
myositis
Nodular fasciitis presents as a rapidly enlarging, tender skin
nodule in the upper limbs of young adults. Aspirates tend
to be cellular with cohesive cell groups having a feathery
edge.[18] Most tumor cells appear stellate with long cytoplasmic
processes [Figure 10]. Nuclei are finely granular with
inconspicuous nucleoli. Ganglion-like cells and inflammatory
cells including foamy macrophages may be found.
Proliferative fasciitis is similar to nodular fasciitis, occurring in
the lower limbs in an older age group than nodular fasciitis.
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Iyer: Cytology of benign soft tissue tumors

Proliferative myositis also affects older individuals in the of ganglion-like cells.[19,20] Atypical spindle cells can also be
shoulder and scapular regions. Aspiration cytology findings seen in myositis ossificans and must not be misdiagnosed
are similar to nodular fasciitis with a more frequent presence as a malignancy.[21] Classical locations and correlation with

Figure 5: Aspirate from leiomyoma showing spindle cells with bluish gray Figure 6: Aspirate from benign Þbrous histiocytoma showing a spindle cell
cytoplasm (MGG, x400) fragment with collagenisation. A histiocytic cell is seen in the upper left
corner of the picture (Pap, x200)

Figure 7: Aspirate from giant cell tumor of tendon sheath showing osteoclas- Figure 8: Aspirate from an inßammatory pseudotumor showing lymphocytic
tic giant cell and a stromal component of spindle cells. Occasional polygonal inßammation and spindle shaped cells with long cytoplasmic processes and
stromal cell is also seen (Pap, x200) marked nuclear pleomorphism (Pap, x400)

Figure 9: Aspirate from atypical Þbroxanthoma showing numerous malignant Figure 10: Aspirate from nodular fasciitis showing cohesive cell groups of
looking cells including tumor giant cells in a myxoid background (Pap, x100) stellate cells with feathery edges (Pap, x200)

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Iyer: Cytology of benign soft tissue tumors
radiography findings are essential for proper diagnosis of
these lesions.
Benign spindle cell tumors: Approach to diagnosis
Aspirates from swellings may not show the typical findings
detailed above and in many instances, it is enough to make
a distinction from malignancy on FNAC rather than give a
precise histological diagnosis. In any aspirate from a spindle
cell lesion, the main criteria to be assessed are cellularity,
nuclear pleomorphism, mitosis, and necrosis. In aspirates
from any tumor showing spindle cell fragments with high
cellularity and/or nuclear pleomorphism in the form of
hyperchromasia or anisonucleosis and/or mitotic figures
and/or presence of necrosis, any one feature should prompt
an inconclusive report making histological examination
mandatory. Aspirates not showing definite necrosis or any
mitosis or clearly pleomorphic nuclei or very high cellularity
should be carefully evaluated to distinguish a low-grade
sarcoma from a benign spindle cell lesion.[22] Even the slightest
increase of cellularity or nuclear chromatin abnormality in
the absence of specific features for one of the above tumors,
should mandate a histological examination.
To conclude, the purpose of FNAC in benign soft tissue
lesions is to be an initial screening test to differentiate from
infective lesions and it should be used to triage patients
requiring early biopsy. The specific diagnosis is almost always
made on histopathology and FNAC should not be used as a
replacement for an excision biopsy. Immunocytochemistry
on aspirates has little role in the evaluation of benign
mesenchymal lesions and will anyway not help to distinguish
between benign and malignant lesions.
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Source of Support: Nil, Conflict of Interest: None declared.