Ovid: Zelger: Am J Surg Pathol, Volume 20(4).April 1996.483-491
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© Lippincott-Raven Publishers
Volume 20(4), April 1996, pp 483-491
Clear Cell Dermatofibroma: Case Report of
an Unusual Fibrohistiocytic Lesion
[Case Report]
Zelger, Bernhard W. M.D.; Steiner, Hansjörg M.D.;
Kutzner, Heinz M.D.
From the Department of Dermatology (B.W.Z.) and Pathology
(H.S.), University of Innsbruck, Innsbruck, Austria, and
Dermatohistopathological Private Laboratory, Friedrichshafen, Germany
(H.K.)
Address correspondence and reprint requests to Dr. Bernhard Zelger,
Department of Dermatology, University of Innsbruck, Anichstraße 35,
A-6020 Innsbruck, Austria.
Abstract
A case of clear cell dermatofibroma is presented. Clinically, a 41-year-old woman exhibited
a hard brown nodule on her instep that was assumed to be a dermatofibroma. Histologically,
more than 90% of the lesion was composed of clear cells. Epidermal hyperplasia and a
storiform arrangement of spindle cells and sclerotic collagen in some foci at the periphery of the
lesion indicated the fibrohistocytic origin. Moreover, prominent vascularity and some bizarre
giant cells in the lower part of the lesion were reminiscent of multinucleate cell
angiohistiocytoma. Of a broad panel of antibodies, the lesion was positive only for Factor XIIIa
(and vimentin). Ultrastructurally, clear-cell changes corresponded to a mostly translucent
cytoplasm, focally with some endoplasmic reticulum and prominent lysosomal structures. A
review of 1,496 dermatofibromas seen during the last 15 years at our institute revealed 12
cases (1%) with similar clear-cell changes in a minor part of the infiltrate (<10%). The
differential diagnosis includes metastases of renal-cell carcinoma, which exhibit more atypia and
mitoses and are positive for epithelial cell markers; clear-cell sarcoma, a lesion of tendons or
aponeurosis with some moderate cytoplasmic melanin deposition and immunoreactivity with
HMB-45; and various non-X histiocytic disorders, such as the predominantly vacuolated type of
juvenile (or adult) xanthogranulomas or papular xanthoma, with a mixed infiltrate of various
types of mononuclear and multinucleate histiocytes positive with a variety of macrophage
markers.
Dermatofibroma is a common benign fibrohistiocytic lesion that occurs most commonly on
the legs of middle-aged women. Because of the wide array of histologic aspects, various other
designations, such as (benign) fibrous histiocytoma, histiocytoma cutis, sclerosing hemangioma,
nodular subepidermal fibrosis, or fibrous xanthoma, have been used synonymously. Over the
last decade, numerous distinctive clinicopathologic variants have been described: deep
penetrating dermatofibroma or dermatofibroma extending into subcutaneous tissue (7); atrophic
dermatofibroma
hemosiderotic
cutaneous
(1);
(12),
(14),
dermatofibroma with monster cells
epithelioid
(16),
(15);
aneurysmal (“angiomatoid”)
and multinucleate cell angiohistiocytoma
atypical (“pseudosarcomatous”)
(4,10),
cellular benign
fibrous histiocytoma associated with hyperlipoproteinemia
(6).
(2),
(17);
(13),
palisading
and cholesterotic
The present case report describes
another variant of fibrohistiocytic tissue response characterized by an abundance of clear cells,
which may cause considerable (differential) diagnostic difficulties.
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CASE REPORT
A 41-year-old woman consulted her general practitioner for a dermal tumor on the instep of
her right leg. The lesion had been present for more than 2 years without a tendency to grow or
change. Clinically, it was described as a hard brown tumor of approximately 2-cm diameter
assumed to be a dermatofibroma. There was no history of trauma or insect bite before the
development of this lesion; her history was otherwise unremarkable. The patient was in good
general health. Following excision (with the histologic differential diagnosis of a secondary
renal-cell carcinoma), internal examination with routine laboratory parameters including urine
analysis, chest radiograph, and abdominal sonography, were normal. The patient remained well
with no recurrence during a follow-up of 2 years.
MATERIALS AND METHODS
Slides and paraffin material were sent to one of us (B.W.Z.) for a second opinion. In
addition to hematoxylin and eosin, Perl's prussian blue stain for iron, melanin, van Gieson,
periodic acid Schiff's, and trichrome stains were performed on semiadjacent sections (4 µm) of
two blocks.
Moreover, immunolabelling with a wide variety of markers was done using a standard
three-step streptavidin biotin complex technique. Markers included Factor XIIIa, Q BEnd10
(CD34); S100 protein, HMB-45, NK1/C3 (CD57); pankeratin, CAM 5.2, carcinoembryonic
antigen, epithelial membrane antigen; HAM56, KP1 (CD68), Ki-M1p (another CD68 epitope),
MAC387 (L1-antigen), lysozyme, [alpha]1-antitrypsin; labelling for the adherence of peanut and
Ulex europeus agglutinin, Factor VIII-related antigen; vimentin, desmin, myoglobin, smooth
muscle actin, HHF-35 (for details of markers, see 19,21). The enzyme product was developed
with 3amino-9ethyl carbazole. The sections were finally counterstained with Harris hematoxylin.
Well-suited negative and positive controls were included in each staining procedure. Moreover,
positive internal controls were present in most specimens.
Ultrastructural studies were performed using two blocks of formalin-fixed,
paraffin-embedded tissue. Selected tumor parts were punched out of the paraffin block,
reembedded in Epon 812, and stained with uranyl acetate/lead citrate in the usual way.
Specimens were scanned with a goniometer-equipped Philips EM 400 electron microscope
operating at 80 KV.
A total of 1,496 dermatofibromas sent to the Dermatohistopathological Laboratory of the
Department of Dermatology, University of Innsbruck, Innsbruck, Austria, during the last 15
years (23) were reviewed for clear-cell change. This laboratory is a primary health care
laboratory with approximately 10,000 to 15,000 specimens per year.
RESULTS
Histology
Specimens of both blocks (with serial sections) revealed identical findings: At scanning
magnification (Fig. 1), the dermis was completely replaced by a faintly stained tumor with a
regular, roundish silhouette, which elevated the hyperplastic epidermis above and abutted on
the subcutis below the lesion. The demarcation was smooth with a small grenz zone toward the
epidermis and a smooth nodular border toward the subcutis with some superficial, scalloped
extensions along preexisting septs. No hemorrhage or necrosis was present. Higher
magnification (Fig. 2) revealed a moderately dense infiltrate of markedly vacuolated to optically
clear cells (>90% of the infiltrate), similar in size to keratinocytes. These oval to polygonal
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cells had well-defined cell borders and round to oval, large (20-25 µm) hypochromatic nuclei
with single prominent, eosinophilic nucleolei. Cells were surrounded by fine to sclerotic collagen
and reticulin fibers, resulting in a lace-like pattern in particular outlined by special stains such as
van Gieson, trichrome (Fig. 3a), and Gomori. No mitoses were seen. Occasional lymphocytes
were interspersed between the clear cells. Sclerosis and lymphocytic infiltration or demarcation
(Fig. 4) were more prominent at the periphery of the lesion, where many of the vacuolated cells
also had a more oval to spindly shape, resulting in a storiform-like pattern. Occasional bizarre
giant cells (Fig. 4b and c), similar to those observed in multinucleate cell angiohistiocytoma (17) or
dermatofibroma with monster cells
(15),
were interspersed in the deep parts of the lesion.
Epidermal hyperplasia with a moderate increase in basal pigmentation, but no sebaceous, hair
follicle, or basal cell carcinoma-like features, was present. The lesion was richly vascularized
with numerous partially ectatic capillaries, but showed no pigment deposition.
FIG. 1. Silhouette of clear-cell dermatofibroma (composite microphotograph). Note the faint
staining of most of the lesion, in contrast to epidermis, adnexal structures, and lower margin.
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FIG. 2. (a-c) Series of close-ups (indicated by arrow in Fig. 1) outlining the marked clear cell
change. Cells are surrounded by fine to sclerotic collagen fibers.
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FIG. 3. (a) Trichrome stain outlines a delicate to prominent, lace-like collagen network around
clear cells. (b) Immunoreactivity for Factor XIIIa (50% of cells) with sparing in cells of
prominent clear cell change. (c) Labeling for CD34 outlining prominent vascularity of the lesion.
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FIG. 4. (a-c) Series of closeups from the lower margin (indicated by arrowhead in Fig. 1)
outlining more typical dermatofibroma features such as storiform spindle-cell changes,
prominent (peripheral) collagen, and lymphohistiocytic response. Note the bizarre giant cells in
higher magnifications.
Immunohistochemistry
Up to 50% of the infiltrate was positive for Factor XIIIa
(Fig. 4b),
with more prominent
labelling in vacuolated than in clear cells and at the periphery of the lesion. Except for vimentin,
the lesion was negative for all other markers, in particular HMB-45 and epithelial and
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macrophage markers, but it revealed prominent vascularity with endothelial cell markers
(Fig.
3c).
Electron microscopy
Clear-cell changes corresponded to a mostly translucent cytoplasm, focally with some
endoplasmatic reticulum and prominent lysosomes, giving these cells a granular appearance.
The cells had large round to oval euchromatic nuclei with prominent nucleoli and were densely
surrounded by collagen fibers.
Review of all 1,496 dermatofibromas sent to our Dermatohistopathologic Unit during the last
15 years revealed 12 cases (1%) with similar clear-cell changes (Fig. 5 and 6) in a minor part
(10%) of the infiltrate. For clinicopathologic details see
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FIG. 5. (a) Silhouette of lower parts from a deep penetrating dermatofibroma. Note more
faintly stained parts, in particular in upper left corner. (b, c) Higher magnifications
(corresponding structures indicated by arrowhead and arrow) reveal focal clear cell change (case
5).
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FIG. 6. (a) Typical example of dermatofibroma. Note more faintly stained areas in lower
dermis (indicated by arrows). (b, c) Higher magnifications from right lower margin
(corresponding structures indicated by arrowheads) reveal prominent clear cell features (case
8).
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TABLE 1. Clinicopathological data of dermatofibromas with focal clear cell changes (cases 1-12)
DISCUSSION
Numerous clinicopathologic variants of dermatofibroma are known for their problems in
delineation from various other (soft tissue) tumors: (a) deep penetrating dermatofibroma (7,22),
which usually occurs on the lower legs of adult women, may mimic dermatofibrosarcoma
protuberans; (b) epitheliod histiocytoma (16), which has a clinically similar profile, Spitz nevi;
(c) cellular benign fibrous histiocytoma
(2),
which prefers the upper extremities of men and has
a high rate of local recurrence, is often confused with dermatofibrosarcoma protuberans or
leiomyosarcoma; (d) atypical (“pseudosarcomatous”) fibrous histiocytoma (4,10) as atypical
fibroxanthoma; (e) aneurysmal (angiomatoid) histiocytoma
(13),
which often presents as a
rapidly growing, tender lesion suspected to be of vascular origin; other examples include: (f)
hemosiderotic histiocytoma (12), which is clinically often assumed to be a (malignant)
melanocytic lesion, or (g) multinucleate cell angiohistiocytoma
(17),
whose grouped violaceous
erythematous papules may mimic Kaposi's sarcoma. The present case expands the spectrum of
difficulties in correctly interpreting the variable findings of fibrohistiocytic tissue response:
Clear-cell features as described in this case might be confused with metastases of renal-cell
carcinoma, clear-cell sarcoma, or various members of the non-X histiocytic family, in particular,
early, predominantly vacuolated types of xanthogranuloma and papular xanthoma. This problem
may be even greater when the clinical situation is not quite so straightforward, as in our case of
a middle-aged woman who presented with a lesion on the lower leg clinically diagnosed as a
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dermatofibroma. In such cases, histology has a decisive input on the benefit and management
of the patient.
Metastases of renal-cell carcinoma
(5)
show a less regular growth pattern with necrosis,
hemorrhages, cellular atypia, and mitoses; moreover, lesions are usually positive with epithelial
markers. Clinically, skin metastases of renal-cell carcinoma before detection of the primary
tumor are rare and occur mostly on the head, in particular, the scalp. Clear-cell sarcoma (3), or
malignant melanoma of soft parts, is a deeply located tumor of tendon sheath or aponeurosis;
an irregular growth of tumor nests and columns is surrounded by a delicate framework of
collagen and reticulin bundles. Cytologically, cells are rather monomorphous, polygonal to
fusiform with focal eosinophilic granulation. In addition, melanin deposition is frequently seen
by Fontana stain, and, interestingly, the lesion is HMB-45 but not S100 protein positive.
Clinically, this tumor prefers the lower legs of adult women (20-40 years). Various non-X
histiocytic disorders, such as the predominantly vacuolated type of juvenile (or adult)
xanthogranulomas (20) or papular xanthoma (18), show a more complex infiltrate of various
types of mononuclear (xanthomatized, spindle-shaped, scalloped, oncocytic) and multinucleated
(Touton) histiocytes that are positive with a variety of macrophage markers. Clinically, these
lesions occur in decreasing frequency on the head, neck, trunk, and extremities. When multiple
and within the first 2 years of life, they are easily recognized; yet solitary lesions in adults may
cause greater diagnostic difficulties. Various other xanthomas (eruptive, tuberous, or
xanthelasma) (9) are characterized by a predominance of xanthomatized cells as well as
(occasional) Touton cells; xanthomas are clinically distinctive lesions, mostly multiple
disseminated with a yellowish color and associated increase of plasma lipid levels. Finally,
balloon cell nevi (11) are rarely intradermal only or without remnants of more typical nevus
cells; moreover, this lesion is always S100 protein positive.
The clear cells in clear-cell dermatofibroma should not be confused with foamy histiocytes
(“fibrous xanthoma”). The latter show no optically clear cells but do show prominent
xanthomatization, which is not present in clear-cell dermatofibroma. A review of the literature
and our own experience suggest that clear-cell dermatofibromas must be quite rare. To the best
of our knowledge, no comparable case has been reported. Only recently, a similar case
occurring on the shoulder of a 42-year-old man was presented in a poster at the American
Society of Dermatology in New Orleans, February 1-3, 1995 (8). Our own studies revealed no
similar case in nearly 1,500 dermatofibromas seen during the last 15 years. Yet clear-cell
change was found in 12 cases (1%) in a minor part of the infiltrate (<10%), documenting that
such a feature represents a possible reaction pattern of dermatofibromas.
In summary, we describe a case of clear-cell dermatofibroma, an unusual and rare
manifestation of fibrohistiocytic tissue response, which might be confused with other clear-cell
entities. We hope our observation will (a) make (dermato)pathologists aware of this lesion,
which may then lead to a better characterization of this phenomenon, and (b) help to avoid this
pitfall of differential diagnoses in clear-cell neoplasms whose misinterpretation, in particular as
metastases of renal-cell carcinoma or clear-cell sarcoma, may lead to marked mismanagement
of and discomfort for patients.
Acknowledgment: We thank Prof. Parwaresch, Department of Pathology, University of
Kiel, Germany, for kindly providing us with the macrophage marker Ki-M1p.
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Key Words: Dermatopathology; Immunohistochemistry, clear cell; Dermatofibroma; Clear
cell neoplasms
Accession Number: 00000478-199604000-00013
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