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enign brous histiocytoma (FH), also known as dermatobroma, is one of the most common soft tissue
tumors of the skin. Cutaneous FH arises in the reticular
dermis but may quite often extend into the supercial
subcutis and typically occurs on the extremities of young
to middle-aged adults.1 In its classic form, cutaneous FH
is composed of mononuclear spindle-shaped or histiocytoid cells arranged in a storiform pattern, with or without
fascicles, and with entrapped collagen bundles at the edge
of the lesion. The stroma is typically variably collagenous
or hyalinized, and variable numbers of admixed chronic
inammatory cells, multinucleate giant cells, and foamy
histiocytes are usually present.2 The papillary dermis is
often spared, resulting in a grenz zone between the lesion
and the overlying epidermis, which is frequently hyperplastic.3 Several morphologic variants of cutaneous FH are
well established, some of which also have distinctive clinical features, including cellular,4 aneurysmal,5,6 atypical,7
clear cell,8 lipidized,9 and epithelioid10,11 types. Although
generally considered a benign tumor, the cellular, aneurysmal, and atypical variants of cutaneous FH have a signicant tendency for local recurrence, with a recurrence
rate of approximately 20% for each of these variants.47
Furthermore, extremely rarely, cutaneous FH can give rise
to metastatic disease. At least 16 well-documented cases of
cutaneous FH with metastasis have been described in the
literature over the last 22 years, mostly as single-case reports. This highly unusual event in cutaneous FH is much
rarer than metastasis of deep brous histiocytoma,
which is a variant of FH that occurs exclusively in deep
soft tissues and has a distinctive morphologic appearance
and a small but signicant risk of metastasis, occurring in
5% in a study of 69 cases.12
The aim of this study was to investigate this unusual
and rare occurrence by studying the clinical and pathologic features of a series of patients with morphologically
benign cutaneous FH that developed metastases.
Am J Surg Pathol
Am J Surg Pathol
RESULTS
Clinical Findings
The clinical ndings are summarized in Table 1.
There were 9 male and 7 female patients in the study
group. Patient age at the time of presentation ranged
from 3 to 68 years, with a mean age of 42 years. Apart
from 1 pediatric patient, all patients were adults (Z23 y).
Primary tumors arose on the lower leg in 3 patients, thigh
in 2, buttock in 1, trunk (back) in 3, shoulder region in 3,
neck in 2, and nger in 1. The primary site was uncertain
for 1 patient (patient 12), who presented with bilateral
axillary masses and lung nodules. Although originally it
was thought that axilla represented the primary tumor
site, clinically and radiologically the axillary masses were
deep and appeared most consistent with lymph nodes.
r
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Am J Surg Pathol
42
Neck
NK Aneurysmal
Yes, 2
24
Metastatic Sites
Time to
Metastasis
(mo)
Lymph node
(cervical-1/51
nodes)
24
24
250
30
Shoulder
1.8
Epithelioid
No
NA
33
Back
Cellular &
atypical
No
NA
Lung (multiple,
bilateral nodules)
24
63
Leg
(lower)
Cellular
Yes, 3
36
Lymph node
(inguinal)
96
Lung (large
unilateral mass)
Soft tissue (satellite
nodules &
preauricular)
Lymph nodes
(axillary-5/10)
Lung (multiple,
bilateral nodules)
Lung (multiple,
bilateral, up to
1.2 cm, nodular
and cystic)
Soft tissue
(supraclavicular)
Lung (multiple
nodules, up to
0.7 cm RUL,
RML, RLL)
Liver
Lung (multiple,
bilateral nodules,
up to 1 cm)
132
41
Shoulder
Aneurysmal
Yes
17
55
Toe
Atypical
Yes
36
62
Back
3.5
Cellular
Yes
11
132
Inguinal
lymphadenectomy
74
95
Surgical resection of
lung metastases
Adriamycin and
ifosfamide
60
17
17
3
Neck
Cellular
No
NA
56
Finger
2.5
Cellular
Yes
1.5
3.5
10
Lower leg NK
Cellular
Yes
11
23
Shoulder
Cellular
No
NA
Lymph nodes
(inguinal; 4/5
nodes)
Lung (bilateral lung
nodules)
Axillary &
supraclavicular
lymphadenopathy, presumed
metastases
clinically
AWD, 132
17
38
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AWD, 264
Surgical resection of
lung metastases
NK
Radiation therapy to
primary site after
second local
recurrence
246
Adjuvant/
Additional
Treatment
Disease
Status
[Follow-up
Duration
(mo)]
<1y
NK (biopsy only of 1
lung lesion)
AWD, 68
DUC, 17
(myocardial
infarction)
NED
NA
AWD,E12
Am J Surg Pathol
TABLE 1. (continued)
Time to
First
Primary Size Histologic
Local
Recurrence
Case Age Sex
Site
(cm)
Type
Recurrence
(mo)
12
51
M Uncertain NK
13
68
14
25
Leg
(upper)
Buttock
NA
NA
NA
Cellular
No
NA
NK
Cellular
Yes, 7
24
Metastatic Sites
Lung (multiple,
bilateral nodules,
up to 2.7 cm)
Lymph nodes
(bilateral axillary,
up to 4.3 cm)
Lung (multiple),
pleura, chest wall
Lymph nodes
(inguinal)
Time to
Metastasis
(mo)
0
NA (biopsies only)
NA
NK
DOD, 10
72
Chemotherapy &
radiation therapy
after 4th local
recurrence
DOD, 96
15
16
31
50
Back
(upper)
Thigh
NK
NK
Cellular &
atypical
Cellular
Yes
Yes, 3
12
156
Intra-abdominal
Lung
Soft tissue (4-5
satellite nodules
from primary
scar site to
shoulder)
Lymph nodes
(axillary, 1/21)
Lymph nodes
(inguinal, 4/14)
Adjuvant/
Additional
Treatment
Disease
Status
[Follow-up
Duration
(mo)]
Additional
chemotherapy after
development of soft
tissue mets
84
12
19
180
No
NED, 186
AWD indicates alive with disease; DOD, died of disease; DUC, dead of unrelated causes; NA, not applicable/not available; NED, no evidence of disease; NK, not
known.
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Am J Surg Pathol
FIGURE 1. Cellular FH (neck, patient 8) with mild overlying epidermal hyperplasia, a Grenz zone (A) and entrapped hyaline
collagen bundles at the edges (B). The growth pattern is mixed fascicular and storiform (C), and the lesional cells are bland,
spindled, and histiocytoid with admixed foam cells (D).
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Am J Surg Pathol
FIGURE 2. Aneurysmal cutaneous FH (shoulder, patient 5) with dilated blood-filled spaces (A). Biopsy of an axillary lymph node
with bland histiocytoid tumor cells associated with prominent stromal hemorrhage, hemosiderin deposition, and cholesterol clefts
(B). Lung metastases in this patient were solid and cystic (C), and the tumor was morphologically similar to the primary
aneurysmal FH (D).
metastatic disease: patient 2 after resection of lung metastases and patient 15 after soft tissue and nodal metastases
(patient 15). Two patients received radiation therapy for
locally recurrent disease (patients 1 and 7). One patient
received both chemotherapy and radiation therapy but died
due to slowly progressive disease 96 months after primary
diagnosis (patient 14).
DISCUSSION
In this report, the clinical and pathologic features of
16 patients with morphologically benign cutaneous FH
that metastasized are described. The primary tumors
showed characteristic features of the cellular, atypical,
aneurysmal, or epithelioid histologic subtypes, the cellular variant being the most commonly encountered (11
of 16 cases). The primary tumors tended to be somewhat
large, with an average size of 3.2 cm but were otherwise
indistinguishable from conventional cutaneous FH
and, as such, lacked any histologic features that might
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Am J Surg Pathol
FIGURE 3. Epithelioid cutaneous FH (shoulder, patient 2) with peripheral entrapment of hyaline collagen bundles (A). Tumor cells
have epithelioid cytomorphology with frequent binucleate forms (B). A subpleural lung nodule (C) in the same patient demonstrates almost identical tumor cell morphology (D) to that in the primary tumor.
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Am J Surg Pathol
FIGURE 4. Cellular FH (back, patient 7) with a mixed fascicular and storiform growth pattern. Multinucleate giant cells were
noted in other areas (A). Needle biopsy of a supraclavicular soft tissue metastasis that developed 1 year after the primary diagnosis
consists of a bland histiocytoid tumor morphologically similar to the primary and also has prominent multinucleate giant cells (B).
The liver tumor also showed a similar storiform proliferation of bland histiocytoid cells (C and D).
interpreting these tumors as other entities, such as dermatobrosarcoma protuberans (DFSP), so-called angiomatoid malignant brous histiocytoma (AMFH), or
unclassied dermal sarcomathat is, a cutaneous tumor
that may fall into the morphologic differential diagnosis
with FH and have recognized metastatic potential. All
cases in this series lacked the monotonous population of
more basophilic spindle cells with high nuclear/cytoplasmic ratio of DFSP. Furthermore, although occasional
cases extended into the superficial subcutis as often happens in FH, none showed the characteristic honeycomb
pattern of invasion into the subcutis or the compact
storiform growth pattern seen in DFSP. AMFH most
commonly arises in superficial subcutaneous tissue, is well
circumscribed, often with a peripheral lymphoid cuff, and
is composed of a monotonous population of tumor cells
with a uniform spindled or oval cytomorphology. The
large dilated pseudovascular spaces of AMFH may mimic
aneurysmal FH, but the above features, in addition to the
presence of one of the characteristic translocations of this
r
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Am J Surg Pathol
FIGURE 5. Cellular FH arising on a finger (patient 9) (A). The tumor recurred locally 6 weeks after initial excision, and the
reexcision also shows classic features of cellular FH (B). Multiple discontiguous nodules developed proximal to the primary tumor,
2 of which are shown here and are morphologically indistinguishable from the primary tumor (C and D).
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logic subtypes in the primary lesions, which lacked morphologic features that may have predicted adverse
outcome and which showed correspondingly similar
morphology in the metastases. In these cases, the primary
tumors included ordinary FH24,28,30 as well as the cellular,13,2529 aneurysmal5,26 or atypical7,26 variants, and,
similar to the current study, the most common metastatic
sites were the lungs and lymph nodes. Lung metastases
were frequently cystic and were originally mistaken as
primary lung tumors because of this.24 Again, similar to
our findings, the interval to metastases in the prior reports was extremely wide, ranging from as short as 4
months26 to up to 23 years from the time of excision of a
cellular FH in 1 case.27 In the current study, the interval
to first metastasis ranged from 0 to 180 months.
Metastasis of histologically benign cutaneous FH
is a clinically aggressive event with substantial morbidity
and mortality. In this series, local recurrence also
occurred in 10 patients, 4 of whom had multiple recurrences. Six patients have so far died of disease, and the
clinical course in these patients was variable with some
r
Am J Surg Pathol
FIGURE 6. Cellular FH (thigh, patient 16) with admixed foamy histiocytes and lymphocytes (A). The local recurrence shows
increased mitotic activity (B; arrows) compared with the initial tumor. The inguinal lymph node metastasis shows typical features
of cellular FH and some dilated blood-filled spaces (C). The cytomorphology of the metastatic tumor is bland, spindled, and
histiocytoid, similar to the initial lesion, with conspicuous mitoses (D).
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Am J Surg Pathol
FIGURE 7. Metastatic tumor in the lung from the primary tumor shown in Figure 1; note the similar storiform and fascicular
growth pattern (A) and cytomorphology (B) to that seen in the primary tumor. The metastatic tumor also contained admixed
foam cells.
1
2
Guillou et al26
De Hertogh et al13*
Kaddu et al7*
1
2
Osborn et al27
Bisceglia et al28
Gu et al29
Szumera-Cieckiewicz and
Ptaszynski30
1
1
Ordinary
NK
Aneurysmal
Cellular
Cellular
Aneurysmal/
atypical
Cellular
Cellular
Cellular
Atypical/cellular
Atypical
Cellular
Cellular
Ordinary
Cellular
Cellular
Ordinary
Local
Recurrence
Metastatic Site(s)
Outcome
Yes
NK
Yes, multiple
Yes, multiple
Yes
No
Lung
Lung
Lymph node
Lung, lymph nodes
Lung, lymph nodes
Lymph node
AWD, 22 y
AWD, 2 y
Case 1 of present study
NED, 9 y
AWD, 15 y
Mets, 19 y
No
Yes, multiple
No
No
Yes
Yes, multiple
NK
Yes, multiple
Yes
No
No
Lymph node
Lymph node
Lung
Lung
Lymph nodes, soft tissues
Lung
Lung
Lymph nodes
Lymph nodes
Lung
Lymph nodes
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Am J Surg Pathol
ACKNOWLEDGMENTS
The authors thank the following pathologists who
kindly contributed case materials and clinical follow-up
information when available: B. Loftus, Amsterdam, The
Netherlands; M-L.F. van Velthuysen, Amsterdam, The
Netherlands; B. Boyce, Rochester, NY; J.Z. Sickel, Rochester, NY; R.E. Nakhleh, Jacksonville, FL; R. Sciot,
Leuven, Belgium; K. Hara, Nagakute-cho, Aichi-gun, Aichiken, Japan; R.F.M. Schapers, Venlo, The Netherlands;
A.P. de Bruine, Venlo, The Netherlands; O. Ben-Izhak,
Haifa, Israel; L.K. Yacoub, Methuen, MA; H. Bai, Methuen, MA; A.L. Uzieblo, Royal Oak, MI; M. Roh, Ann
Arbor, MI; S. Dudley-Walker, Hattiesburg, MS; R.H.
Byrd, Tulsa, OK; N. Saxena, Peoria, IL; T. Zhang, West
Palm Beach, FL; A. van Lenders, Rotterdam, The Netherlands; A. Mackay, Chester, UK; D. Eakins, Norfolk, UK;
R. Cawley, Portland, ME; A. Nahal, Montreal, Canada.
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