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Case report

Pseudoangiosarcomatous squamous cell

carcinoma developing on a burn scar: A case
report and review of the literature

Sung Hoon Koh a, Suk Joon Oh b,*, Huan Chun b, Seon Gyu Kim b
a
Department of Plastic and Reconstructive Surgery, Hallym University Sacred Heart Hospital, Anyangsi, Republic of Korea
b
Institute of Burn, Reconstructive Plastic Surgery, Bestian Seoul Hospital, Seoul, Republic of Korea

article info abstract

Article history: Pseudoangiosarcomatous squamous cell carcinoma, also known as pseudovascular, pseu-
Accepted 21 February 2014 dovascular adenoid and pseudoangiomatous squamous cell carcinoma, is an exceedingly
rare, aggressive variant of cutaneous squamous cell carcinoma with extreme acantholysis
Keywords: resulting in angiosarcoma-like areas. Histologically, a pseudoangiosarcomatous pattern
Pseudoangiosarcomatous includes complex anastomosing channels and spaces lined with neoplastic cells. The
Squamous cell carcinoma neoplastic cells exhibit cytokeratin and vimentin positivity but yield negative results with
Burn scar CD31 and CD34. This case report describes pseudoangiosarcomatous squamous cell carci-
Skin transplantation noma developing on a burn scar on the ankle. In this report, we emphasize the importance
Artificial dermis of establishing a diagnosis with histological and immunohistochemical examination, and
we review the described incidence of the age and sites with the prognosis for the treatment
of pseudoangiosarcomatous squamous cell carcinoma of the skin.
# 2014 Elsevier Ltd and ISBI. All rights reserved.

The pseudoangiosarcomatous variant of squamous cell
carcinoma (SCC) exhibits inter-anastomosing cellular cords
that simulate vascular proliferation and it was first described
by Eusebi et al. [1] in 1986 as a form of mammary carcinoma.
Six cases of cutaneous pseudovascular adenoid squamous cell
carcinoma of the skin as a different variant from adenoid SCC
were reported by Nappi et al. [2] in 1992. Banerjee et al. [3] in
1992 described three cases of carcinoma mimicking angio-
sarcoma occurring on the skin. These studies [2,3] described
the first pseudoangiosarcomatous SCC of the skin. This
pseudoangiosarcomatous SCC has been reported in different
organs, such as breast, lung and bladder [1,3,5].
In contrast to the typical clinical appearance of angiosar-
coma, pseudovascular adenoid SCC presented itself as a
discrete cutaneous ulcer or crusted tan pink nodule. Micro-
scopically, the lesion was characterized by interanastomosing
cord-like arrays of polygonal or flattened tumor cells, with
internal pseudolumina that contained detached tumor cells.
Immunohistochemically, all cases of pseudovascular adenoid
SCC were reactive with antibodies to cytokeratin. In addition,
none were immunoreactive for Factor VIII-related antigen,
and two of the three studied for CD 34-reactivity were also
negative. Pseudovascular adenoid SCC may be distinguished
effectively from angiosarcoma of the skin by attention to its

* Corresponding author at: Institute of Burn, Reconstructive Plastic Surgery, Bestian Seoul Hospital, 429 Dogok-ro Gangnam-gu, Seoul 135-
998, Republic of Korea. Tel.: +82 10 5308 2009; fax: +82 70 7005 4230.
E-mail addresses: sjoh46@nate.com, sjoh46@hotmail.com (S.J. Oh).
http://dx.doi.org/10.1016/j.burns.2014.02.019
0305-4179/# 2014 Elsevier Ltd and ISBI. All rights reserved.

Please cite this article in press as: Koh SH, et al. Pseudoangiosarcomatous squamous cell carcinoma developing on a burn scar: A case report and
review of the literature. Burns (2014), http://dx.doi.org/10.1016/j.burns.2014.02.019
JBUR-4312; No. of Pages 6

e2 burns xxx (2014) xxx.e1–xxx.e6

Fig. 1 – A 64-year-old Korean woman noted a smoothly-raised reddish tumor occupying a 5 T 7 cm ulcerated bed of the
postero-lateral aspect of the right ankle (A). The Achilles tendon was exposed at the upper portion of wound defect after a
wide excision of the ulcerative tumor (B). A MetriDermW sheet (5 T 5 cm in size) covered the wound bed (C). This photograph
shows the postoperative appearance 8 months after MetriDermW and thin split-thickness skin grafting (D).

clinical features and appropriate immunohistochemical stud-
ies [2].
We describe a new case of pseudoangiosarcomatous SCC
developing on a burn scar ulcer of the ankle, in which the
diagnosis depended upon careful histological and immuno-
histochemical assessment of the excised tumor.
1. Case
A 65-year-old Korean woman was seen for ulceration on the
lateral aspect of her right ankle. When she was 30 years old,
she had suffered a flame burn that covered her right lower
extremity. A burn scar was formed on the lateral aspect of her
right leg and ankle. When she was 60 years old, an ulcerative
lesion appeared on the lateral aspect of her right ankle.
Recurrent ulcerations of her right ankle had been cared for
with conservative therapy by herself. She had undergone a
cholecystectomy for an adenocarcinoma of the gallbladder 2
weeks previously in the other university hospital. She initially
visited our department for ulcer treatment of her right ankle
before the postoperative chemotherapy of an adenocarcinoma
of the gall bladder. The authors suspected that a Marjolin’s
ulcer developed from the burn scar, and recommended a
preoperative biopsy. However, the patient refused the preop-
erative histologic study.
An ulceration of her right ankle, 5  7 cm in size, had been
worsening for the previous 4 months. A smoothly -raised
reddish tumor occupied the ulcerative bed (Fig. 1A). The scar
surrounding the ulceration was dyspigmented. The inguinal
and popliteal lymph nodes were not palpable. Positron
emission tomography (PET) and computerized tomography
(CT) could not detect any metastases.
Surgery was performed under general anesthesia. The
ulcerative area was marked just outside the areas of
dyspigmentation using a surgical marking pen. A wound
bed of 8  12 cm in size after excision of the lesion exposed the
Achilles tendon (Fig. 1B). The pathologist reported that the
resection margins of a surgical specimen were free of tumor
cells. Bleeding was meticulously controlled by electrical
coagulation. The wound defect was covered with an acellular
elastin dermal substitute (1 mm thick; MatriDerm1; Dr.
Suwelack Skin & Health Care AG, Josepf-Suwelack Straße,
48727 Billerbeck, Germany) (Fig. 1C). A Zimmer Air Dermatome
(Zimmer Inc., Warsaw, IN, USA) was then used for harvesting a
thin 0.008 inch (0.2 mm) skin graft from the lateral aspect of
the right thigh. The thin skin graft was then simultaneously
applied to the MetriDerm1 -grafted region and fixed with skin
staples. Tiny perforations were made in the skin graft to
prevent fluid accumulation. The grafts were dressed with
Bactigras Paraffin Gauze (Smith & Nephew Medical Ltd., Hull,
UK) and covered with gauze sponges moistened with saline
solution. The lower extremity was dressed with a circumfer-
ential elastic wrap and immobilized with a short leg plaster
splint. During the postoperative course, approximately 20% of
the skin graft was partly lost. However, an additional thin skin
graft completely healed the wound defect 50 days after the
first surgery (Fig. 1D). The authors recommended that the
patient wear a pressure garment stocking and well-fitted soft
shoes. Postoperative results showed a good appearance
(Fig. 1D) and no metastatic findings by PET 8 months after
the surgery.

Please cite this article in press as: Koh SH, et al. Pseudoangiosarcomatous squamous cell carcinoma developing on a burn scar: A case report and
review of the literature. Burns (2014), http://dx.doi.org/10.1016/j.burns.2014.02.019
JBUR-4312; No. of Pages 6

burns xxx (2014) xxx.e1–xxx.e6 e3

Fig. 2 – A low-power photomicrograph shows the transition from squamous epithelial nests in the margin of the ulcer to the
pseudoangiosarcomatous space in the elevated tumor over the ulcer bed (H&E stain, 100T) (A). A high-power
photomicrograph of complex anastomosing channels and spaces lined with neoplastic cells mimicking the histopathologic
features of angiosarcoma (H&E stain, 400T) (B).

Histologically, a transitional area of squamous cell carci-
noma was observed that had a pseudoangiosarcomatous
pattern with the formation of numerous, small, cystic spaces
and channels lined with plump neoplastic cells (Fig. 2A). Most
of the spaces appeared empty, but some contained pale,
faintly basophilic material. Occasional spaces showed de-
tached floating tumor cells. The channels appeared to
intercommunicate, producing complex, anastomosing laby-
rinthine structures (Fig. 2B).
In the immunohistochemical examination, the tumors
positively stained with anti-cytokeratin antibody CK (AE1/AE3,
DAKO, Denmark) (Fig. 3A). However, this tumor yielded
negative results with CD31 (JC70A, DAKO, Denmark) (Fig. 3B)
and CD 34 (QBEnd10, DAKO, Denmark) (Fig. 3C). The
endothelial cells of normal vessels were positive for CD31
and CD34 (Fig. 3B and C). This tumor was also strongly positive
for vimentin (V9, DAKO, Denmark) (Fig. 3D).
2. Discussion
Pseudoangiosarcomatous SCC of the skin mimics an angio-
sarcoma. Table 1 summarizes pseudoangiosarcomatous SCC
of the skin in the English literature. A total of 19 patients,
including 11 men and 8 women, have been described [2–12].
The mean age was 69 years (range, 43–86 years). Pseudoan-

Fig. 3 – A high-power photomicrograph of the transition area; squamous epithelial nests and neoplastic cells lining complex
anastomosing spaces exhibit positivity for CK (400T) (A). A high-power photomicrograph of complex anastomosing
channels and spaces; the neoplastic cells are negative for CD31 (B) and CD34 (C) (endothelial cell markers) staining, but
endothelial cells of normal vessels reveal CD31and CD34 positivity (400T). Photomicrograph of a section stained with anti-
vimentin antibody. The neoplastic cells are positive for vimentin (400T) (D).

Please cite this article in press as: Koh SH, et al. Pseudoangiosarcomatous squamous cell carcinoma developing on a burn scar: A case report and
review of the literature. Burns (2014), http://dx.doi.org/10.1016/j.burns.2014.02.019
JBUR-4312; No. of Pages 6

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Table 1 – Chronological summary of pseudoangiosarcomatous SCC developing on the skin.

Author Sex Age Site Clinical Immunohisto- Treatment F/U information
[reference] (years) (greatest findings chemical
dimen- examination
sion, cm)
Nappi et al. [2] M (n = 5), 53 Face (>1.5) Tan-pink no- Positive; CK (n = 5). Excision, lym- DOD with lung, bone
F (n = 1) dule, ulcer EMA (n = 5), VIM phadenectomy, and regional LN
immunocom- (n = 3): chemotherapy metastasis within
promised Negative; FVIII (n = 5), in DOD (n = 3) 4 years
CD34 (n = 3)

46 Hand (>1.5) Immunocom- DOD with lung, bone

promised and regional LN me-
tastasis within 4
years
Others Neck, face, Excision in AWD DOD (tumor size, >
mean, hand, leg (n = 3) 1.5 cm) with lung,
65.3 bone and regional
LN metastasis with-
in 4 years
5 years AWD (n = 3,
tumor size, <1.5 cm)
Banerjee et al. M 78 Ear (1.5) Focal ulcer Positive; CK (1), CK Radical exci- 5 years 9 months,
[3] (AE1/3), VIM: sion, RT DOD with cervical
Negative; FVIII, CD34, and mediastinal LN
UEA (1) metastasis
M 82 Face (1.8) Focal ulcer Positive; CK (1), CK Biopsy, RT AWD
(AE1/3), VIM:
Negative; FVIII, CD34,
UEA (1)
M 64 Perineum Polypoid, focal Positive; CK (1), CK Excision 4 months, DOD with
(6) ulcer in urethral (AE1/3): lung metastasis
fistula Negative; FVIII, VIM,
CD34, UEA (1)
Cox et al. [4] M 43 Face (1) Nodule ulcer Negative; CK, FVIII, Excision, local NS
VIM, S100, Desmin recurred- RT)
F 82 Leg (NS) Nodules in ve- Positive; CK (1,3), VIM: Biopsy, amputa- NS
nous ulcer Negative; FVIII tion
Pitt et al. [5] F 84 Vulva (4) Fungating palp- Positive; CK (AE1/ Radical vulvect- 3.2 months, DOD
able LNs 3,CAM5.2): omy and ILND with perineal ab-
Negative; CD34, FVIII, scess
CD31, S100
Yamamoto F 86 Face (1.2) Dome-shape Positive; CK (34bE12): Excision 3 years, AWD
et al. [6] cherry-red Negative; CD34, FVIII,
VIM, EMA, S100
Fujio et al. [7] M 74 Face (2) Reddish ele- Positive; CK: Excision, RT 8 months, DOD with
vated Negative; FVIII lung and preauricu-
lar LN metastasis
Nagore et al. [8] M 69 Ear (4) Exophytic,cher- Positive; Pan-CK: Excision, RND, 8 months, DOD with
ry-red palpable Negative; CD31, CD34, RT, Chemo lung metastasis
cervical LNs VIM, S100, FVIII
Conde-Taboada F 79 Sacrum (NS) Exophytic with Positive; CK (strong), Biopsy 4 months, DOD, in-
et al. [9] decubitus ulcer EMA: tra-pelvic organ me-
palpable LNs, Negative; CD31, CD34, tastasis
FVIII
Santos et al. F 78 Vulva (5) Exophytic, nod- Positive; CK (AE1/ Radical vulvect- 5 months, AWD
[10] ular pink with 3,34bE12), EMA: omy and BI LND,
ulcer, palpable Negative; CD31, CD34, RT
LNs FVIII, CAM5.2, CEA,
Desmin, SMA
Horn et al. [11] F 57 Vulva (1) Exophytic ulcer, Positive; CK (AE1/3, Radical vulvect- 4 months, DOD with
Palpable LNs MNF116): omy and lung metastasis
Negative; CD31, CD34, BIFLND, Chemo
FVIII, VIM

Please cite this article in press as: Koh SH, et al. Pseudoangiosarcomatous squamous cell carcinoma developing on a burn scar: A case report and
review of the literature. Burns (2014), http://dx.doi.org/10.1016/j.burns.2014.02.019
JBUR-4312; No. of Pages 6
burns xxx (2014) xxx.e1–xxx.e6
Table 1 (Continued )
Author Sex Age Site Clinical
[reference] (years) (greatest findings
dimen-
sion, cm)
Olaofe et al. [12] F 75 Leg (16) Nodular old
scar ulcer
Present case F 65 Ankle (7) Reddish eleva-
tion within burn
scar ulcer
SCC, squamous cell carcinoma; NS, not stated; LN, lymph node; n, number; CK, cytokeratin; VIM, vimentin; FVIII, Factor VIII; RT, radiotherapy;
Chemo, chemotherapy; ILND, inguinal lymph node dissection; BILND, bilateral inguinal lymph node dissection; RND, radical neck dissection;
BIFLND, bilateral inguinal femoral lymph node dissection; F/U, follow up; AWD indicates alive without evidence of disease; DOD, dead of
disease.
giosarcomatous SCC involved the skin of the face (n = 6) [2,4,7],
ear (n = 2) [3,8], leg (n = 3) [2,4,12], vulva (n = 3) [5,10,11], neck
(n = 1) [2], hand (n = 1) [2], perineum (n = 1) [3], and sacrum
(n = 1)[9] adjacent to a decubitus ulcer. Furthermore, the skin
tumors were associated with a venous leg ulcer (n = 1) [4], an
old surgical scar on the leg (n = 1) [12], a urethral fistula of the
perineum (n = 1) [3] and a sacral decubitus ulcer (n = 1) [9]. This
tumor may occur in young immunocompromised adults after
renal transplantation with a poor prognosis [2].
Histologically, the tumor architecture varies from area to
area, but two main growth patterns were recognized, with
transition zones where the two patterns blended being the
rule. These two growth patterns are designated spongiotic and
spindle cell. The spongiotic pattern is characterized by
channels of varying size with frequent anastomoses resulting
in the formation of an intricate network strongly reminiscent
of a vascular neoplasm. In the spindle cell areas, easily
recognizable channels do not form. These areas are arranged
in more compact bundles organized in multiple directions
resulting in an interweaving pattern [1]. Careful examination
of the skin tumors revealed some focal areas with evident
transition from squamous nests to more acantholytic areas
extending toward the pseudovascular spaces [8]. The alcian
blue preparation revealed the presence of hyaluronic acid in
most of the pseudovascular channels and cystic spaces in the
tumors and in the intracytoplasmic vacuoles [3]. Hyaluroni-
dase-sensitive and hyaluronidase-resistant acid mucopoly-
saccharide were also found in the intercellular compartment
[3]. In our case, two main growth patterns were recognized – a
squamous nest pattern in the ulcer margin and a pseudoan-
giosarcomatous pattern of complex anastomosing channels
and spaces lined with polygonal or flattened tumor cells over
the ulcer bed-, and a transition zone where the two patterns
blended was prevalent (Fig. 2A and B). Histochemical
examination of the present case was not studied.
Immunohistochemical examinations are therefore essen-
tial to achieve an accurate diagnosis. Pseudoangiosarcoma-
tous/pseudovascular SCC is determined by positive staining
with one or more monoclonal antibodies to cytokeratin (CK),
with the exception of one case [4] in the English literature [1–
12]. The vascular markers CD31, CD34 and factor VIII-related
Please cite this article in press as: Koh SH, et al. Pseudoangiosarcomatous squamous cell carcinoma developing on a burn scar: A case report and
review of the literature. Burns (2014), http://dx.doi.org/10.1016/j.burns.2014.02.019
e5
Immunohisto- Treatment F/U information
chemical
examination
Positive; CK, VIM: Excision NS
Negative: CD34, S100,
EMA
Positive; CK (AE1/3), Excision 8 months, AWD
VIM (V9):
Negative;CD31
(JC70A),
CD34 (QBEnd10)
antigen are consistently negative, although in some cases [2–
4,12], especially less differentiated cases, vimentin may be
positive. The neoplastic cells in the present case were positive
for cytokeratin and vimentin, but yielded negative results for
CD31 and CD34 (Fig. 3A–D).
The degree of morbidity and mortality in pseudoangiosar-
comatous SCC is higher than in other variants of SCC, perhaps
due to its anaplastic histology. Death with lung metastasis
(n = 7) occurred in 10 of the 19 cases of the skin reviewed in the
English literature (Table 1). The presence of regional palpable
lymph nodes (n = 7), immune compromise (n = 2) [2], tumor
size greater than 1.5 cm (n = 2) [2], and ear (n = 2) [3,8], vulva
(n = 2) [5,11], perineum (n = 1) [3] or sacrum involvement (n = 1)
[9] seem to indicate a poor prognosis. These observations
imply that this tumor is highly aggressive and requires prompt
and radical treatment. This tumor must be examined to
discover the lesion early when it is treatable. Radical excision
is necessary. Adjuvant radiotherapy and possibly chemother-
apy may be considered in these cases [8].
The biological behavior of pseudoangiosarcomatous SCC
is difficult to assess as limited follow-up data have been
reported. The follow-up period of the present case was too
short to allow us to comment on the behavior. Therefore,
whether the biologic behavior of pseudoangiosarcomatous
SCC is different from that of conventional squamous cell
carcinoma that develops on a burn scar remains unknown.
To the best of our knowledge, pseudoangiosarcomatous
SCC on burn scars has not been described in the English
literature. Pseudoangiosarcomatous SCC in the present case
can be documented as a variant of SCC that developed on a
burn scar.
3. Conflict of interest statement
None declared.
Acknowledgement
No source of funding.
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review of the literature. Burns (2014), http://dx.doi.org/10.1016/j.burns.2014.02.019
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