Case 5 -
Spindle Cell Lesion, Consistent with Dermatofibrosarcoma Protuberans (DFSP)
Celeste N. Powers
Virginia Commonwealth University
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A 22 year old African American male presented with a history of a slowly enlarging occipital scalp lesion. He had been incarcerated for almost one year. His past medical history is unremarkable with the exception that he remembered he had been "hit over the head with a bottle" in a fight one year previously. The physical examination revealed a visibly ulcerated nodule that was tender to palpation. Superficial fine needle aspiration was performed without difficulty or complication.
Case 5 - Figure 1
Scan magnification of Diff Quik stained aspirate smear showing high cellularity. Densely packed fragments of monotonous cells with adipose tissue interspersed are noted. The background is relatively clean.
Case 5 - Figure 2
Low power magnification Diff Quik stained aspirate smear. Scattered storiform fragments are noted. Lightly metachromatic stroma is seen at the edges of these dense fragments. The cell have oval nuclei vary slightly in size and have delicate cytoplasm.
Case 5 - Figure 3
Low power magnification of Papanicolaou stained smear. Storiform frgments, densely packed, with bland nuclei and light even chromatin, small nucleoli are occasionally visible.
Case 5 - Figure 4
Higher magnification of Diff Quik stained smear shown in Figure 5-2.
Case 5 - Figure 5
High power magnification of Papanicolaou stained smear showing an isolated storifom fragment. Cytoplasmic processes are better apreciated as well as distinct small nucleoli. Pleomorphism is minimal.
Case 5 - Figure 6
High power magnification of a Diff Quik stained smear. The small dark oval nuclei most likely represent endothelial cells of capillaries that traverse the fragments. The metachromatic, fibrillar stroma is best seen at the edges of the fragment.
Case 5 - Figure 7
Higest magnification of Figure 5-6. Note uniformity of nuclei with homogeneous chromatin.
Case 5 - Figure 8
Additional image. CT scan of lesion. Note this protuberant lesin is present on the occiptal scalp and is well circumscribed.
Case 5 - Figure 9
Additional image. Low power magnification of an H&E stained section of the cell block from the needle rinse of the aspirated material showing a storiform fragment of cohesive fibrohistiocytic spindle cells with entrapped adipose tissue.
Case 5 - Figure 10
Additional image Gross photo of resection specimen that highlights the circumscription and nodularity of the lesion as well as its location in the tissue above the occipital bone.
Case 5 - Figure 11
Additional image Low power magnification of an H&E stained section of the resection specimen. The storiform pattern as well as delicate vasculature of this lesion can be seen.
Case 5 - Figure 12
Additional image High power magnification of an H&E stained section from the resection specimen illustrating the monotony of the fibrohistiocytic cells. A rare mitosis is seen.
Spindle cell lesions of the head and neck are quite diverse, ranging from reactive lesions to benign
and malignant tumors. The cytomorphology of these various lesions can overlap significantly, such that
specific diagnoses are challenging if not impossible. The importance of accurate clinical and radiologic
information as well as ancillary techniques can not be over emphasized. This case will illustrate a
difficult spindle cell lesion that was accurately diagnosed based on the synthesis of data available and
the presence of pathologists on site to perform the aspiration.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Figures 5-1 through 5-7 illustrate this case. Figure 5- 8 is a photograph of the lesion prior to FNA.
The aspirate smears were of moderately high cellularity with scattered individual and storiform arrays of
spindle cells with interspersed fibrillar stroma. The background revealed a modest amount of blood and
adipose tissue was seen entrapped within the larger storiform fragments. The latter feature was best
appreciated at low magnification. The stroma is highlighted on the Diff Quik stain as a metachromatic
finely fibrillar matrix. Embedded within this stroma are variable numbers of bland spindle cells with
moderate amount of cytoplasm but with ill defined cell boundaries. Inconspicuous capillaries often
traverse the larger fragments. The spindle cell nuclei are variably sized with smooth nuclear membranes
and fine homogenous chromatin. Small distinct nuclei or chromocenters were usually present and enhanced
by the Papanicolaou stain. Very little pleomorphism was observed. Mitotic figures were scarce and never
atypical. With the exception of modest amount of blood the background was clean without myxoid or
mucinous features, inflammation or necrosis. Figure 5-9 is a low magnification of the cell block
obtained from needle rinses. The cell block showed a storiform pattern of dense and loosely packed
spindle cells with foci of entrapped adipocytes. No ancillary studies were performed at the time of the
diagnosis since the clinical history, physical examination and imaging studies supported our cytologic
impression of a fibrohistiocytic lesion and we were able to suggest a specific diagnosis. The patient
had the lesion surgically resected, margins were negative and short term follow up, uneventful. Figure
5-10 shows a gross photo of the resected specimen; Figures 5-11 and 5-12 show representative histology.
If this same situation occurred today,immunohistochemistry would have been performed on the cell block
(which would probably be a core biopsy!). A typical IHC panel would include CD34 and actin as well as
other specific markers depending on the differential diagnosis(e.g. S-100, cytokeratin, HMB-45, CD99
etc). For educational purposes the following IHC results would have been obtained: CD34: positive;
actin, S-100, HMB-45, CD-99, desmin, cytokeratin: negative.
The differential diagnosis for a spindle cell lesion of the head and neck obtained by FNA is quite
intimidating. Interpretation by cytomorphology alone becomes very difficult when trying to classify the
lesions beyond the non-neoplastic and benign and malignant tumor categories. Perhaps a better approach
that is more successful is to classify lesions into benign-low grade which includes reactive/inflammatory
lesions as well as benign neoplasms and high grade which is predominantly sarcomas and less frequently
spindle cell carcinomas. The availability of mini-biopsies by aspiration needles and true "needle core
biopsies" that usually guarantee a good sample of the lesion, especially if done with ultrasound or
imaging guidance, helps provide a histologic perspective as well as material for ancillary studies, for
the most part immunochemistry (IHC). With this potential information available a more specific
subclassification or diagnosis can usually be rendered. However, there can still be significant overlap
both cytologically and histologically with spindle cell lesions, even when IHC is brought into play, such
that excision for definitive diagnosis will be recommended. In the case presented herein, the
differential diagnosis, based on a generic impression of spindle cell cytomorphology, will include the
lesions listed below. A close study of the nuclear morphology may suggest further classification of cell
type as fibroblastic, fibrohistiocytic, neural, muscular. Obviously clinical presentation and radiologic
imaging as well as IHC will be exceptionally helpful in excluding many of these lesions as well.
Mesenchymal reactive/reparative process Nodular fasciitis Fibromatosis Fibrous histiocytoma Schwannoma
Leiomyoma Dermatofibrosarcoma protuberans Low grade fibrosarcoma Synovial Sarcoma Malignant fibrous
histiocytoma Leiomyosarcoma Malignant peripheral nerve sheath tumor (MPNST) Spindle cell carcinoma
Spindle cell lesion, consistent with dermatofibrosarcoma protuberans (DFSP)
Typically the cytopathologist who performs an FNA of a DFSP is usually confronted with a patient who
has a firm, nodular (protuberant) cutaneous mass often in trunk or arms rather than head and neck, that
has been slowly growing often for a period of years. There may be a history of antecedent trauma. In
the case described above the lesion was quite distinctive and clearly protuberant! Figure 5-8. The
patient was a African American male with a history of trauma in that region. With the physical
examination and that history, DFSP quickly entered the differential. With any spindle cell or soft
tissue lesion the initial classification of the aspirate begins with clinical history and physical
examination. Any prior lesions or significant history? Where is the lesion anatomically? Is the mass
large or small, superficial or deep? Is it painful? Is there surface discoloration or a scar? When the
aspiration is performed is it easy to obtain material? Does the patient feel pain? Is there excessive
bleeding? Finally, when reviewing the material microscopically you have already built a differential,
adding the cytomorphologic clues helps refine the differential further. Cellularity, pattern and
background elements can all be assessed at low magnification. If it is a spindle cell lesion the next
order of business if to attempt to identify the origin of the predominant cell type. In this case the
recognition that the cells comprising the lesion are fibrohistiocytic rather than neural or muscular was
helped by the shape of the nuclei. Reactive fibroblasts have angulated nuclei while those of DFSP tend
to be round to oval. Nuclei of smooth muscle cells are typical described as cigar shaped with blunt ends
while those from neural lesions may be twisted, slender or elongate. In this case the aspirate was quite
cellular with scattered fragments of densely packed cells arranged in a storiform pattern. Inflammation
and necrosis were absent.Many of these fragments revealed entrapped adipose tissue and delicate network
of capillaries. The individual cell nuclei were bland and round to oval suggesting a fibrohistiocytic
origin. These features in conjunction with the physical examination and history were key clues in
recognizing this lesion as a DFSP. At the time, this case helped to define some of the cytologic
criteria useful in the diagnosis of DFSP. These criteria were then used prospectively in future
aspirations of this lesion. These subsequent cases formed a series we published in 1993 that elucidated
the helpful features seen on aspirates of DFSP. See attachment. A pitfall that may infrequently arise
is the occurrence of frank sarcomatous change of DFSPs that may be sampled during aspiration. Areas of
fibrosarcoma and malignant fibrous histiocytoma can be found in initial, as well as recurrent DFSPs and
are associated with a less favorable prognosis. Of course the converse is also problematic but not
recognized until rersection, because FNA samples very limited and discreet areas, especially in larger
masses, sarcomatous change can be missed entirely on aspiration (sampling error). Thus, the histologic
variability of some of these tumors requires multiple FNA's with sampling from different areas. Imaging
can be very helpful in locating these different regions for sampling. DFSP will more often have a
consistent cytologic pattern from multiple samples. Fortunately, it is unlikely that the standard
surgical treatment for DFSP will adversely affect the patient in either case. In the workup of the
differential diagnosis for this case and DFSP in general, attention to cytologic detail, especially
recognition of low magnification patterns and background elements as well as nuclear shape is important
to guide the subsequent workup. Although IHC can be used successfully on direct smears and monolayer
preparations it is preferred to utilize cell blocks and core biopsies- obtaining needle core biopsies
during "FNA" is now routine practice in most regions. If sufficient material is obtained IHC can be used
successfully to distinguish many lesions of neural or muscular origin, although it is less useful in
attempts to distinguish the variety of fibrohistiocytic lesions that may be encountered as superficial
dermal masses as indicated in the following sections. CD 34, while relatively non-specific, is still
useful in IHC panels for spindle cell tumors and should be included as a positive marker for DFSP in IHC
panels that will typically include CD68, SM Actin, desmin, S-100, EMA, Cytokeratins (and possibly
vimentin to confirm immunoreactivity). Remember that IHC is most useful when there is a panel such that
there is a good positive as well as negative- look for internal controls as well as the standard
laboratory controls run with the case. Based on cytomorphology alone, nodular fasciitis (NF), is the
most troublesome soft-tissue pseudotumor that may be difficult to distinguish from DFSP. Although the
spindle cells of both entities can vary in size and shape, the proliferating fibroblasts of NF tend to
have nuclei with less rounded, more angular and prominent nucleoli. Both lesions also tend to have
varying amounts of myxoid matrix; however, there is a more haphazard ("tissue culture") arrangement of
the cells within the matrix in NF, as well as an intermingling of inflammatory cells (leucocytes,
eosinophils, and macrophages). Another similar spindle cell tumor is the spectrum of lesions termed
fibrous histiocytoma (dermatofibroma, histiocytoma, sclerosing hemangioma). Fibrous histiocytomas may
occur in the deep (noncutaneous) soft tissues as well as skin and subcutis. Hemosiderin deposits within
these cutaneous masses may result in red to brown discoloration of the overlying skin. This may help
clinically to distinguish them from DFSP. Aspirates from these masses produce stromal fragments of
increased cell density and less intercellular matrix. In addition, background elements that may be
present include plump histiocytes and multinucleate tumor giant cells that are often pigment laden, as
well as inflammatory cells. The presence of entrapped adipose tissue suggests an infiltrative pattern as
seen in DFSP, rather than the more circumscribed histiocytoma. Fibromatosis and low-grade fibrosarcoma
are also problematic especially since an adequate sample is sometimes difficult to obtain because of
tight cellular cohesion. The cytologic features of these fibroblasts can vary considerably, from the
deceptively bland low-grade sarcoma to the worrisome nuclear pleomorphism of aggressive fibromatosis.
IHC can be very helpful in differentiating these lesions. Although at the time this case was active CD34
was not used in the work up of DFSP; in combination with actin it can help distinguish between NF,
fibrous histiocytoma and fibromatosis (CD34 negative, actin positive) and DFSP ( CD34 positive; actin
negative). Both benign and malignant peripheral nerve sheath tumors can overlap cytologically with DFSP.
Nuclear shape is useful in cases of neurofibroma where the nuclei are often described as resembling a
fish hook or as twisted. Many of these aspirates will be paucicellular. Aspirates of schwannomas are
variably cellular with cells arrayed in fascicles. The recognition of palisading nuclei that comprise
the Verocay bodies is helpful. Ancient change can be worrisome but will not be diffuse. IHC is quite
useful here since there is intense positive staining with S-100 protein. In malignant peripheral nerve
sheath tumors S-100 staining can be very focal and less intense, here cytomorphology is useful. These
spindle cells typically are haphazardly arrayed with oval or fusiform hyperchromatic nuclei and long
fibrillary cytoplasmic processes. Stroma when observed will also be delicate and fibrillary. A sarcoma
occurs in younger adults in the head and neck region (as well as extremities and trunk) is fibrosarcoma.
Aspirates from low grade lesions are not as cellular as those form higher grade tumors. Spindle cells
are often in bundles and become more mitotically active and discohesive and obviously malignant with
increasing grade. Nuclei again are bland oval and have a moderate amount of cytoplasm often with
cytoplasmic processes in the lower grade tumors. Synovial sarcoma is a high grade tumor, usually in
younger patient near joints, that will show short, bland spindle cells with scant cytoplasm and oval to
round uniform nuclei with micronucleoli in sheets and clusters typically without a storiform pattern.
Glandular formations may be seen in biphasic lesions however, sampling will be an issue. IHC and
cytogenetics can confirm this diagnosis. CD99 positivity is seen and, if biphasic, focal EMA and keratin
may be seen as well. Cytogenetic analysis will reveal a t(X;18) (p 11;q11) and the molecular marker is
fusion of SYT-SSX . Malignant fibrous histiocytoma (MFH) is another high grade sarcoma that although it
has a storiform pattern will have significant pleomorphism, multinucleated giant cells, atypical mitoses
and often necrosis. Although less likely to be confused cytologically with DFSP, spindle cell melanoma
should be in the differential. Aspirates from these lesions may show pleomorphic spindle cells, but with
minimal stroma and no discernible storiform pattern. Studies have shown that spindle cell melanomas are
less likely to show the cytologic features of classical melanoma (i.e. intranuclear inclusions, pigment,
macronucleoli). In addition they are also less likely to be strongly positive for melanoma markers-
although S-100 still remains the most sensitive marker, followed by HMB-45. Similarly another infrequent
mimic of spindle cell tumors is the spindle cell carcinoma. At the time of diagnosis clinical,
radiologic, and cytologic data were the mainstay in the diagnosis of fibrohistiocytic lesions.
Cellblocks from needle rinses rather than core biopsies were typical. After the success of having
suggested the correct diagnosis in this case, further cases were diagnosed and a series which defined the
criteria was published. With time the difficulties and pitfalls were soon apparent- nodular fasciitis
was the most problematic of the differential diagnoses. This resulted in a second publication shortly
thereafter describing the pitfalls inherent in the cytopathologic diagnosis of spindle cell tumors!
Fortunately, progress on other fronts was made. CD 34 became a mainstay in the confirmation and
distinction of DFSP from its more benign fibrohistiocytic counterparts. Imaging studies are now
incredibly sophisticated and replace much of the information garnered from excisional biopsies and
resections such that chemotherapy and radiation can be performed preoperatively. Cytogenetic analysis
and the discovery of fusion gene products in DFSP and many other soft tissue tumors allow for specific
classification if material is available. Molecular analysis and separation of soft tissue tumors for
targeted therapy is here. However- fine needle aspiration is still the most effective and safe technique
for retrieval of sufficient material to perform cytologic triage that includes classification and often
subclassification so the appropriate ancillary tests are performed.
Review of the Literature/Treatment Options (if applicable):
Dermatofibrosarcoma protuberans (DFSP) is a low to intermediate grade fibrohistiocytic neoplasm that
typically involves the dermis and subcutis. This tumor usually presents in adults between 20-30 years of
age, although it can occur in children and the elderly. Its incidence is low, 2-6% of soft tissue
sarcomas, interestingly this incidence is doubled among blacks. DFSP has an indolent course as a slow
growing nodule that develops over months to years. Yet is locally aggressive which accounts for its
propensity for local recurrence. Metastases are rare and usually occur late in the course of the
disease, often after several local recurrences. Initially appearing as a cutaneous thickening, this
lesion will develop into a larger, fungating nodule and when growth extends into the epidermis ulceration
may occur. While the trunk is the most common location for DFSP approximately 14% occur in the head and
neck. The histopathology of DFSP is simply characterized by CD 34 positive spindle cells arranged in a
storiform pattern. Most DFSP (90%) exhibit an unbalanced translocation t (17;22) where the
platelet-derived growth factor-B gene (PDGFB) of chromosome 22 is fused with the collagen 1 alpha 1 gene
(COL1A1) of chromosome 17. From the cytologic perspective a diagnosis of DFSP by fine needle aspiration
can still pose a challenge, as it falls into the very broad differential of spindle cell lesions.
Although a description of metastatic DFSP to the lung was described in 1996 by Perry et al, it was not
until 1993 that Powers et al characterized the spectrum of FNA findings in a series of six cases.
Subsequently there have been additional series and case reports published that further highlight the
diagnostic difficulty of this lesion. Surgery is mainstay of treatment and due to the frequency of local
recurrence (11-53%) current recommendations call for 2-4 cm margins using conventional surgery. Mohs'
surgery has yielded good results with significantly lower recurrence rates. There are also reports of
radiation therapy being used with success. Prognosis is excellent but does decrease significantly with
identification of metastases.
Soft-tissue tumors, particularly those of fibrohistiocytic origin, may be difficult to accurately
diagnose by aspiration cytology. The presence of stromal fragments in aspirate smears or cell block
sections allows not only examination of individual cell morphology but recognition of distinctive
patterns, that in conjunction with good clinical data, are helpful in the subclassification of these
lesions. Cytologic features useful in the diagnosis of DFSP include storiform arrays of bland spindle
cells, presence of entrapped adipose tissue, and lack of background elements such as inflammatory cells.
Although clinical correlation and /or IHC may be very helpful in a majority of cases, there are instances
when a specific diagnosis may not be possible. In these cases, a more general diagnosis such as
"spindle-cell tumor" or "mesenchymal lesion" with a list of probable diagnoses may have to suffice.
Selected references on treatment
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