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122 Sangüeza and Requena / Pathology of Vascular Skin Lesions
13. Albrecht S, Kahn HJ. Immunohistochemistry of intravascular papillary endothelial hyperplasia. J Cutan
Pathol 1990;17:16–21.
14. Rosai J, Akerman LR. Intravascular atypical vascular proliferation. Arch Dermatol 1974;109:704–17.
15. Cooper PH. Vascular tumors. In: Farmer R, Hood AF, eds. Pathology of the Skin. Norwalk, CT, Appleton
& Lange, 1990:804–46.
16. Pins MR, Rosenthal DI, Springfield DS, Rosemberg AE. Florid extravascular papillary endothelial
hyperplasia (Masson’s pseudoangiosarcoma) presenting as a soft-tissue sarcoma. Arch Pathol Lab Med
1993;117:259–63.
17. Chen KT. Extravascular papillary endothelial hyperplasia. J Surg Oncol 1987;36:52–4.
18. Borrelli L, Ciniglio M, Faffulli N, Del Torto M. Intravascular papillary endothelial hyperplasia in the
hand of a fencer. Pathologica 1992;84:551–6.
19. Inaloz HS, Patel G, Knight AG. Recurrent intravascular papillary endothelial hyperplasia developing
from a pyogenic granuloma. J Eur Acad Dermatol Venereol 2000;15:156–8.
20. Hashimoto H, Daimaru Y, Enjoji M. Intravascular papillary endothelial hyperplasia. A clinicopatho-
logic study of 91 cases. Am J Dermatopathol 1983;5:539–46.
21. Heyden G, Dahl I, Angervall L. Intravascular papillary endothelial hyperplasia in the oral mucosa. Oral
Surg Oral Med Oral Pathol 1978;45:83–7.
22. Buchner A, Merrell PW, Carpenter WM, Leider AS. Oral intravascular papillary endothelial hyperpla-
sia. J Oral Pathol Med 1990;19:419–22.
23. Stern Y, Braslavsky D, Shpitzer T, Feinmesser R. Papillary endothelial hyperplasia in the tongue: a
benign lesion that may be mistaken for angiosarcoma. J Otolaryngol 1994;23:81–3.
24. Tosios K, Koutlas IG, Papanicolaou SI. Intravascular papillary endothelial hyperplasia of the oral soft
tissues: report of 18 cases and review of the literature. J Oral Maxillofac Surg 1994;52:1263–8.
25. De Courten A, Fuffer R, Samson J, Lombardi T. Intravascular papillary endothelial hyperplasia of the
mouth: report of six cases and literature review. Oral Dis 1999;5:175–8.
26. Wehbe MA, Otto NR. Intravascular papillary endothelial hyperplasia in the hand. J Hand Surg [Am]
1986;11:275–9.
27. Schwartz IS, Parris A. Cutaneous intravascular papillary endothelial hyperplasia: a benign lesion that
may simulate angiosarcoma. Cutis 1982;29:66–9.
28. Dekio S, Tsujino Y, Jidoi J. Intravascular papillary endothelial hyperplasia on the penis: report of a case.

J Dermatol 1993;20:10:657–9.
29. Cisco RW, McCormac RM. Intravascular papillary endothelial hyperplasia of the foot. J Foot Ankle
Surg 1994;33:610–6.
30. Kato H. Two cases of intravascular papillary endothelial hyperplasia developing on the sole. J Dermatol
1996;23:655–7.
31. Stewart M, Smoller BR. Multiple lesions of intravascular papillary endothelial hyperplasia (Masson’s
lesions). Arch Pathol Lab Med 1994;118:315–6.
32. Romani J, Puig L, Costa I, de Moragas JM. Masson’s intravascular papillary endothelial hyperplasia
mimicking Stewart-Treves syndrome: report of a case. Cutis 1997;59:148–50.
33. Renshaw AA, Rosai J. Benign atypical vascular lesions of the lip. A study of 12 cases. Am J Surg Pathol
1993;17:557–65.
34. Levere SM, Barsky SH, Meals RA. Intravascular papillary endothelial hyperplasia: a neoplastic “actor”
representing an exaggerated attempt at recanalization mediated by basic fibroblast growth factor. J Hand
Surg [Am] 1994;19:559–64.
35. Katzman B, Caliguri DA, Klein DM, Nicastri AD, Chen P. Recurrent intravascular papillary endothelial
hyperplasia. J Hand Surg [Br] 1997;22:113–5.
36. Yamamoto T, Marui T, Mizuno K. Recurrent intravascular papillary endothelial hyperplasia of the toes.
Dermatology 2000;200:72–4.
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Chapter 7 / Cutaneous Vascular Hyperplasias 123
6. PSEUDO-KAPOSI’S SARCOMA
Pseudo-Kaposi’s sarcoma is an unfortunate term applied to two completely different
processes, acroangiodermatitis of Mali and the Stewart-Bluefarb syndrome. Acroangio-
dermatitis of Mali (1) refers to skin lesions on the lower extremities of patients with
chronic venous insufficiency, and Stewart-Bluefarb syndrome (2) is an arteriovenous
malformation that clinically resembles Kaposi’s sarcoma.
Clinical Features
Clinically, the Stewart-Bluefarb syndrome usually presents early in life and involves
the lower extremities of young adults unilaterally (Fig. 13). Purple papules and macules
appear, which in some instances are painful and become ulcerated. The affected limb may

have an increased temperature, with varicose veins, and a palpable thrill can be felt as an
expression of the underlying arteriovenous shunt. Similar changes have been described
at the site of cutaneous shunts for hemodyalisis (3–5) (Figs. 14 and 15) in paralyzed
extremities (6,7) and in patients with Klippel-Trenaunay syndrome (8,9). Acroangio-
dermatitis of Mali is simply exaggerated stasis dermatitis. The lesions are usually bilat-
eral and develop in elderly patients with chronic venous insufficiency (Fig. 16). They
have a predilection for the dorsal aspect of the feet and ankles. The lesions begin as
violaceous macules and patches that develop slowly into soft, nontender, red to purple
papules and nodules. Patients also present with scaly and indurated purple plaques, and
Fig. 13. Stewart-Bluefarb syndrome in the lower extremity of young male patient. An underlying
arteriovenous shunt was present.
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124 Sangüeza and Requena / Pathology of Vascular Skin Lesions
changes of stasis dermatitis are evident on the adjacent skin. Lesions identical to those
of acroangiodermatitis of Mali may be seen in the distal part of an amputation stump
(10,11) (Fig. 17) induced by a suction-socket prosthesis (12).
H
ISTOPATHOLOGIC FEATURES
Both types of pseudo-Kaposi’s sarcoma resemble Kaposi’s sarcoma clinically, but
histopathologically they are completely different. In the Mali’s variant, the histopatho-
logic findings are those of stasis dermatitis, namely, there is an increased number of thick-
walled vessels lined by plump endothelial cells, extravasation of erythrocytes, and
deposits of hemosiderin (Fig. 18). These changes are confined to the upper half of the
dermis. In Stewart-Bluefarb syndrome, the entire dermis may be affected and, in large
specimens, an arteriovenous shunt may be identified. Histopathologically, the differen-
tial diagnosis with early stages of Kaposi’s sarcoma is usually straightforward, keeping
in mind that the patch and plaque stages of Kaposi’s sarcoma are characterized by a
proliferation of irregular jagged blood vessels, which are present around preexisting
venules and adnexa and are lined by thin endothelial cells. As a rule, the papillary dermis
is spared in the early stages of Kaposi’s sarcoma. Recently, the expression of CD34

antigen has been proposed as a feature to histopathologically distinguish lesions of
pseudo-Kaposi’s sarcoma from authentic Kaposi’s sarcoma. CD34 positivity is detected
in both endothelial cells and perivascular spindle cells of Kaposi’s sarcoma, whereas no
such expression is seen in pseudo-Kaposi’s sarcoma (13). Furthermore; HHV-8 is not
demonstrated in lesions of pseudo-Kaposi’s sarcoma (14).
Fig. 14. Acroangiodermatitis involving the forearm and the hand, distally to the site of a cutaneous
arteriovenous shunt for hemodialysis.
Fig. 15. Acroangiodermatitis involving the inner aspect of the forearm distally to the site of a
cutaneous arteriovenous shunt for hemodialysis. The lesion showed the appearance of a purpu-
ric plaque.
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Chapter 7 / Cutaneous Vascular Hyperplasias 125
Fig. 16. Acroangiodermatitis of Mali involving the inner aspect of the ankle of an elderly male.
Fig. 17. Acroangiodermatitis of Mali involving the distal part of an amputation stump.
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126 Sangüeza and Requena / Pathology of Vascular Skin Lesions
TREATMENT
Treatment of acroangiodermatitis of Mali is unsatisfactory and often unnecessary. If
it is required, treatment of venous insufficiency of the lower extremities may be followed
by slow improvement of the cutaneous lesions. Patients with Stewart-Bluefarb syndrome
should consult with a vascular surgeon in order to embolize or excise the arteriovenous
shunt under angiographic control (15).
References
1. Mali JWH, Kuiper JT, Hamers AA. Acro-angiodermatitis of the foot. Arch Dermatol 1965;92:515–8.
2. Bluefarb SM, Adams LA. Arteriovenous malformation with angiodermatitis. Stasis dermatitis simulat-
ing Kaposi’s disease. Arch Dermatol 1967;96:176–81.
3. Goldblum OM, Kraus E, Bronner AK. Pseudo-Kaposi’s sarcoma of the hand associated with an acquired,
iatrogenic arteriovenous fistula. Arch Dermatol 1985;121:1038–40.
4. Landthaler M, Stolz W, Eckert F, Schmoeckel C, Braun-Falco O. Pseudo-Kaposi’s sarcoma occurring
after placement of arteriovenous shunt. A case report with DNA content analysis. J Am Acad Dermatol

1989;21:499–505.
Fig. 18. Histopathologic features of acroangiodermatitis. (A) Scanning magnification show lobu-
lar proliferations of capillaries at the superficial dermis. (B) Higher magnification demonstrates
that the lobules are composed of plump endothelial cells with extravasation of erythrocytes and
deposits of hemosiderin.
07/Sangüeza/99-132/F 01/14/2003, 12:12 PM126
Chapter 7 / Cutaneous Vascular Hyperplasias 127
5. Kim TH, Kim KH, Kang JS, Kim JH, Hwang IY. Pseudo-Kaposi’s sarcoma associated with acquired
arteriovenous fistula. J Dermatol 1997;24:28–33.
6. Meynadier J, Malbos S, Guilhon JJ, et al. Pseudo-angiosarcomatose de Kaposi sur membre paralytique.
Dermatologica 1980;16:190–7.
7. Landthaler M, Langehenke H, Holzmann H, Braun Falco O. Akroangiodermatitis Mali (“Pseudo-
Kaposi”) and gelähmten Beinen. Hautarzt 1988;39:304–7.
8. Lund Kofoed M, Klemp P, Thestrup-Pedersen K. The Klippel-Trenaunay syndrome with acro-
angiodermatitis (pseudo-Kaposi’s sarcoma). Acta Derm Venereol 1985;65:75–7.
9. Lyle WG, Given KS. Acroangiodermatitis (pseudo-Kaposi’s sarcoma) associated with Klippel-
Trenaunay syndrome. Ann Plast Surg 1996;37:654–6.
10. Kolde G, Wörheide J, Baumgartner R, Bröcker EB. Kaposi-like acroangiodermatitis in an above-knee
amputation stump. Br J Dermatol 1989;120:575–80.
11. Gucluer H, Gurbuz O, Kotiloglu E. Kaposi-like acroangiodermatitis in an amputee. Br J Dermatol
1999;141:380–1.
12. Badell A, Marcoval J, Graells J, Moreno A, Peyri J. Kaposi-like acroangiodermatitis induced by a
suction-socket prosthesis. Br J Dermatol 1994;131:915–7.
13. Kanitakis J, Narvaez D, Claudy A. Expression of the CD34 antigen distinguishes Kaposi’s sarcoma from
pseudo-Kaposi’s sarcoma (acroangiodermatitis). Br J Dermatol 1996;134:44–6.
14. Krengel S, Goerdt S, Kruger K, Schnitzler P, Geiss M, Tebbe B, Blume-Peytavi U, Orfanos CE.
Kaposiforme, HHV-8-negative Akroangiodermatitis bei chronisch-venoser insuffizienz. Hautarzt
1999;50:208–13.
15. Utermann S, Kahle B, Petzoldt D. Erfolgreiche Langzeittherapie bei Stewart-Bluefarb-Syndrom.
Hautarzt 2000;51:336–9.

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7. REACTIVE ANGIOENDOTHELIOMATOSIS
Angioendotheliomatosis is a broad term that encompasses two different processes,
one malignant and the other benign. Malignant angioendotheliomatosis is an intravascu-
lar form of malignant lymphoma, whereas the reactive or benign form of angio-
endotheliomatosis is a self-limited intravascular proliferation of endothelial cells that
occurs in the skin as a response to a different stimuli (1).
C
LINICAL FEATURES
Reactive angioendotheliomatosis is usually limited to the skin, and, in contrast to what
was initially thought, is not necessarily associated with an underlying infection. Cases of
reactive angioendotheliomatosis have been described in patients with subacute bacterial
endocarditis, Chagas’ disease, allergic response to cow’s milk protein, pulmonary tuber-
culosis, cryoproteinemia, chronic lymphatic leukemia, hepatopathy and hypertensive
portal gastropathy, antiphospholipid syndrome, rheumatoid arthritis, dermal amyloid
angiopathy, and severe peripheral vascular atherosclerotic disease, but also in patients
with no underlying disease (2–16).
Clinically, the lesions appear as red-brown or violaceous nodules or plaques over the
face (Fig. 19), arms, and legs (2). In addition, petecchiae, ecchymoses, and small areas
Fig. 19. Reactive angioendotheliomatosis in a patient with cryoglobulinemia. Purpuric plaques on
the cheeks of an elderly woman.
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Chapter 7 / Cutaneous Vascular Hyperplasias 129
of necrosis are frequently observed (3,5). The pathogenesis remains unclear, but a circu-
lating angiogenic factor has been proposed by some investigators (4,6). Wick and
Rocamora (1) suggested that reactive angioendotheliomatosis is an unusual residual of
leukocytoclastic vasculitis. In cases associated with cryoglobulinemia or cold aggluti-
nins, the luminal deposits of cryoproteins may be the stimulus to induce the proliferation
of endothelial cells (7,17). A similar pathogenesis has been proposed for glomeruloid

hemangioma in POEMS syndrome (18).
Reactive intravascular angiomatosis of the skin with local deposits of intravascular
immunoglobulin resulting in a vascular proliferation with a glomeruloid pattern has also
been described in patients with monoclonal gammopathy and chronic lymphocytic
B-leukemia (19). In the cases of peripheral atherosclerotic disease, vascular insufficiency
from the occluded arteries appears to be the inciting factor for the endothelial proliferation,
because when the blood flow is restored by a graft bypass, the lesions resolve (8,20). We
have seen examples of both intravascular and diffuse dermal reactive angioendo-
theliomatosis that appeared in acral areas of the forearm and hand secondary to iatrogenic
arteriovenous fistulas for hemodialysis that resolved when the arteriovenous fistula was
removed. We postulated that a local increase of vascular endothelial growth factor, as is the
case in hypoxia, was the cause of the endothelial proliferation (21). Kunstfeld et al. (22)
have recently described an example of diffuse dermal reactive angioendotheliomatosis with
lesions involving the trunk in a patient undergoing chronic hemodialysis.
H
ISTOPATHOLOGIC FEATURES
Histopathologically, the intravascular form of reactive angioendotheliomatosis exhib-
its dilated blood vessels that contain a proliferation of endothelial cells often occluding
the lumina of the vessels; occasionally there are associated fibrin thrombi (Fig. 20).
Focally, recanalized “glomeruloid” blood vessels are seen, especially in the cases asso-
ciated with cryoglobulinemia (7,17). Endothelial cells do not show atypia, and mitotic
figures are not identified. Involved vessels are surrounded by a scanty inflammatory
infiltrate of lymphocytes, neutrophils, and extravasated erythrocytes. In the cases of
reactive angioendotheliomatosis associated with severe peripheral vascular atheroscle-
rotic disease, the histopathologic picture is different. In these cases the proliferation is not
localized to preexisting vessels, or if it is, proliferation is minimal; what is more promi-
nent is the presence of diffuse, interstitial proliferations of endothelial cells that percolate
between the collagen bundles of the reticular dermis (8,20–23).
Immunohistochemical studies have demonstrated that the proliferating cells in reactive
angioendotheliomatosis are endothelial cells, because they expressed factor VIII-related

antigen, Ulex europaeus I lectin, CD34, CD31, and vimentin, but they failed to express
leukocyte antigens such as leukocyte common antigen, LN2, MT1, UCHL1, and L26, as
well as epithelial membrane antigen and cytokeratins (1,7,8,18,22). In some cases, pro-
liferation of pericytic myoepithelial cells, identified by their staining with antibodies to
muscle-associated proteins, are present within and around affected blood vessels (1,9,22).
In rare instances of intravascular reactive angioendotheliomatosis, the proliferating
intravascular cells did not mark with endothelial cell markers but with markers of histio-
cytic differentiation; for this type of lesion the term of intravascular histiocytosis has been
proposed (24,25). PCRs carried out in paraffin-embedded sections of reactive angioendo-
theliomatosis for HHV-8 DNA have been negative (22).
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130 Sangüeza and Requena / Pathology of Vascular Skin Lesions
TREATMENT
Cutaneous lesions of reactive angioendotheliomatosis require no treatment; most of
them regress spontaneously when the cause is eliminated. In two recently described cases
of diffuse dermal reactive angioendotheliomatosis, the lesions responded respectively to
treatment with oral methylprednisolone (22) and isotretinoin (23).
Fig. 20. Histopathologic features of reactive angioendotheliomatosis. (A) Low power shows
numerous vascular structures scattered at different levels of the dermis. (B) Higher magnification
demonstrates plump endothelial cells and fibrin thrombi occluding the lumina of the vessels. (C)
Immunohistochemical studies reveal that most of the endothelial cells express immunoreactivity
for CD31.
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Chapter 7 / Cutaneous Vascular Hyperplasias 131
References
1. Wick MR, Rocamora A. Reactive and malignant “angioendotheliomatosis”: a discriminant clinico-
pathologic study. J Cutan Pathol 1988;15:260–71.
2. Pleger L, Tappeiner I. Zuz kenntnis der systemisierteu Endotheliomatose der cutanen Blutgefasse
(Reticuloendotheliose?). Hautarzt 1959;10:359–63.
3. Ruiter M, Mandema E. New cutaneous syndrome in subacute bacterial endocarditis. Arch Inten Med

1964;113:283–90.
4. Pasyk K, Depowski M. Proliferating systemized angioendotheliomatosis of a 5-month- old infant. Arch
Dermatol 1978;114:1512–5.
5. Gottron HA, Nickolowski W. Extrarenale Löhlein Herdnephritis der Haut bei Endocarditis. Arch Klin
Exp Dermatol 1958;207:156–76.
6. Person JR. Systemic angioendotheliomatosis. A possible disorder of a circulating angiogenic factor.
Br J Dermatol 1977;96:329–31.
7. LeBoit PE, Solomon AR, Santa Cruz DJ, Wick MR. Angiomatosis with luminal cryoprotein deposition.
J Am Acad Dermatol 1992;27:969–73.
8. Krell JM, Sanchez RL, Solomon AR. Diffuse dermal angiomatosis: a variant of reactive cutaneous
angioendotheliomatosis. J Cutan Pathol 1994;21:363–70.
9. Lazova R, Slater C, Scott G. Reactive angioendotheliomatosis. Case report and review of the literature.
Am J Dermatopathol 1996;18:63–9.
10. Martin S, Pitcher D, Tschen J, Wolf JE Jr. Reactive angioendotheliomatosis. J Am Acad Dermatol
1980;2:117–23.
11. Schmidt K, Hartig C, Stadler R. Reaktive Angioendotheliomatose bei chronisch lymphatischer
Leukamie. Hautartz 1996;47:550–5.
12. Quinn TR, Alora MB, Momtaz KT, Taylor CR. Reactive angioendotheliomatosis with underlying
hepatopathy and hypertensive portal gastropathy. Int J Dermatol 1998;37:382–5.
13. Creamer D, Black MM, Calonje E. Reactive angioendotheliomatosis with the antiphospholipid syn-
drome. J Am Acad Dermatol 2000;42:903–6.
14. Tomasini C, Soro E, Pippione M. Angioendotheliomatosis in a woman with rheumatoid arthritis. Am
J Dermatopathol 2000;22:334–8.
15. Ortonne N, Vignon-Pennamen MD, Majdalani G, Pinquier L, Janin A. Reactive angioendotheliomatosis
secondary to dermal amyloid angiopathy. Am J Dermatopathol 2001;23:315–9.
16. Brazzelli V, Baldini F, Vasallo C, et al. Reactive angioendotheliomatosis in an infant. Am J
Dermatopathol 1999;21:42–5.
17. Porras-Luque JI, Fernandez-Herrera J, Dauden E, Fraga J, Fernández-Villalta MJ, García-Díez A.
Cutaneous necrosis by cold agglutinins associated with glomeruloid reactive angioendotheliomatosis.
Br J Dermatol 1998;139:1068–72.

18. Chan JKC, Fletcher CDM, Hicklin GA, et al. Glomeruloid hemangioma: a distinctive cutaneous lesion of
multicentric Castleman’s disease associated with POEMS syndrome. Am J Surg Pathol 1990;14:1036–46.
19. Salama SS, Jenkin P. Angiomatosis of skin with local intravascular immunoglobulin deposits, associ-
ated with monoclonal gammopathy. A potential cutaneous marker for B-chronic lymphocytic leukemia.
A report of unusual case with immunohistochemical and immunofluorescence correlation and review
of the literature. J Cutan Pathol 1999;26:206–12.
20. Kimyai-Asadi A, Nousari HC, Ketabchi N, Henneberry JM, Costarangos C. Diffuse dermal angioma-
tosis: a variant of reactive angioendotheliomatosis associated with atherosclerosis. J Am Acad Dermatol
1999;40:257–9.
21. Requena L, Fariña MC, Renedo G, Alvarez A, Sanchez Yus E, Sangueza OP. Intravascular and diffuse
dermal reactive angioendotheliomatosis secondary to iatrogenic arteriovenous fistulas. J Cutan Pathol
1999;26:159–64.
22. Kunstfeld R, Petzelbauer P. A unique case of benign disseminated angioproliferation combining fea-
tures of Kaposi’s sarcoma and diffuse dermal angioendotheliomatosis. J Am Acad Dermatol
2001;45:601–5.
23. McLaughlin ER, Morris R, Weiss SW, Arbiser JL. Diffuse dermal angiomatosis of the breast: response
to isotretinoin. J Am Acad Dermatol 2001;45:462–5.
24. O’Grady JT, Shahidullah H, Doherty VR, Al-Nafussi A. Intravascular histiocytosis. Histopathology
1994;24:265-8.
25. Rieger E, Soyer HP, LeBoit PE, Metze D, Slovak R, Kerl H. Reactive angioendotheliomatosis or
intravascular histiocytosis? An immunohistochemical and ultrastructural study in two cases of intravas-
cular histiocytic cell proliferation. Br J Dermatol 1999;140:497–504.
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Chapter 8 / Benign Neoplasms 133
133
8
Benign Neoplasms
CONTENTS

ANGIOMA SERPIGINOSUM
INFANTILE HEMANGIOMAS
CHERRY ANGIOMAS (SENILE ANGIOMAS)
A
RTERIOVENOUS HEMANGIOMA
HOBNAIL HEMANGIOMA (TARGETOID HEMOSIDEROTIC HEMANGIOMA)
M
ICROVENULAR HEMANGIOMA
TUFTED ANGIOMA
GLOMERULOID HEMANGIOMA
ACQUIRED ELASTOTIC HEMANGIOMA
KAPOSIFORM HEMANGIOENDOTHELIOMA
SINUSOIDAL HEMANGIOMA
GIANT CELL ANGIOBLASTOMA
SPINDLE CELL HEMANGIOMA (FORMERLY SPINDLE CELL
HEMANGIOENDOTHELIOMA)
B
ENIGN LYMPHANGIOENDOTHELIOMA
BENIGN VASCULAR PROLIFERATIONS IN IRRADIATED SKIN
GLOMUS TUMORS
HEMANGIOPERICYTOMA
CUTANEOUS MYOFIBROMA
1. ANGIOMA SERPIGINOSUM
Hutchinson (1) first described angioma serpiginosum in 1889, under the term “a
peculiar form of a serpiginous and infective nevoid disease.” He used the term “infective”
to describe the pattern of progression of the disease, rather than to suggest an infectious
etiology. Angioma serpiginosum is a neoplasm characterized by a proliferation of endot-
helial cells and formation of new capillaries and not simply a dilation of preexisting
capillaries, as in telangiectases (2). Therefore, this lesion is included among the benign
vascular neoplasms.

C
LINICAL FEATURES
Clinically, the lesions of angioma serpiginosum are characterized by multiple, minute,
red to purple grouped macules that extend over a period of months to years in a serpigi-
nous and gyrate patterns (3).There is no evidence of inflammation, hemorrhage, or pig-
mentation, although the purple points do not blanch completely after the application of
pressure, which could cause the misinterpretation of the lesions as purpura (4). In doubt-
ful cases, epiluminescence microscopy has been proposed as a helpful technique in
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134 Sangüeza and Requena / Pathology of Vascular Skin Lesions
distinguishing angioma serpiginosum from purpuric dermatoses (5). Frequently, there is
a background of diffuse erythema. The condition is asymptomatic and occurs predomi-
nantly in young females, starting in childhood. Most cases are sporadic, but two families
affected by angioma serpiginosum with an autosomal dominant inheritance have been
reported (6). The lesion has a predilection for the extremities, most frequently the lower
limbs (7,8) (Fig. 1), although cases involving extensive areas of the trunk and extremities
have been also described (9). It is usually unilateral, at least initially, but when bilateral
involvement is present, it shows an asymmetric distribution. In rare cases, the lesions may
follow the Blaschko lines (10). Occasionally, angioma serpiginosum may involve the
ocular and nervous system (11). After an initial period of growth, the lesions usually
remain stable in adult life, and sometimes there is partial or complete regression (12). A
group of lesions that has been described as atypical angioma serpiginosum are better
interpreted as superficial hyperkeratotic vascular malformations (13).
H
ISTOPATHOLOGIC FEATURES
Histopathologically, angioma serpiginosum consists of clusters of dilated capillaries
housed in the dermal papillae and lined by thick walls (Fig. 2). An inflammatory infiltrate
is characteristically absent (14–17). Ultrastructural studies have demonstrated in the
thick-walled vessels ectasias of the arteriolar type (18) that are composed of two layers:
an inner layer consisting of a delicate fibrillary material and the outer layer composed of

collagen bundles (19,20). The presence of numerous concentrically arranged pericytes
has also been described (20).
T
REATMENT
In some cases spontaneous and complete regression of the lesion occurs. When this is
not the case good cosmetic results have been reported after treatment of lesions of angioma
serpiginosum with laser therapy (21,22).
References
1. Hutchinson J. A peculiar form of serpiginosum and infective naevoid disease. Arch Surg 1889;1:275.
2. Neumann E. Some new observations on the genesis of angioma serpiginosum. Acta Derm Venereol
1971;51:194–8.
Fig. 1. Clinical appearance of angioma serpiginosum. Multiple minute red-purple grouped macules.
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Chapter 8 / Benign Neoplasms 135
Fig. 2. Histopathologic features of angioma serpiginosum. (A) Low power shows capillary blood
vessels involving the dermal papillae. (B) Higher magnification shows that these grouped capil-
lary blood vessels have thick walls.
3. Stevenson MJ, Lincoln CS. Angioma serpiginosum. Arch Dermatol 1967;95:16–22.
4. Cox NH, Paterson WD. Angioma serpiginosum: a simulator of purpura. Postgrad Med J 1991;67:
1065–6.
5. Ohnishi T, Nagayama T, Morita T, et al. Angioma serpiginosum: a report of 2 cases identified using
epiluminescence microscopy. Arch Dermatol 1999;135:1366–8.
6. Marriott PJ, Munro DD, Ryan T. Angioma serpiginosum—familial incidence. Br J Dermatol 1975;
93:701–6.
7. Yaffee HS. Angioma serpiginosum. Arch Dermatol 1967;95:667.
8. Thiers H, Moulin G. Angiome serpigineux de Hutchinson. Bull Soc Fr Dermatol Syphiligr 1969;76:138.
9. Katta R, Wagner A. Angioma serpiginosum with extensive cutaneous involvement. J Am Acad Dermatol
2000;42:384–5.
10. Gerbig AW, Zala L, Hunziker T. Angioma serpiginosum, eine Hautveranderung entlang den Blaschko-
Linien? Hautarzt 1995;46:847–9.

11. Gautier-Smith PC, Sanders MD, Sanderson KV. Ocular and nervous system involvement in angioma
serpiginosum. Br J Ophthalmol 1971;55:433–43.
12. Litoux P. Angiome serpigineux (deux observations). Bull Soc Fr Dermatol Syphiligr 1969;76:54.
13. Michalowski R, Urban J. Atypical angioma serpiginosum: a case report. Dermatologica 1982;
164:331–7.
14. Baker LP, Sachs PM. Angioma serpiginosum. Arch Dermatol 1965;92:613–20.
15. Burda A, Piechocki M. Uber das sogenannte Angioma serpiginosum. Hautarzt 1968;19:499–504.
16. Barabasch R, Baur M. Angioma serpiginosum. Ein Name für verschiedene dermatologische
Krankheitsbilder. Hautarzt 1971;22:436–42.
17. Laugier P. L’angiome serpigineux de Hutchinson. Dermatologica 1967;135:369–74.
18. Reymond JL, Stoebner P, Amblard P. Telangiectasies naevoides acquises. Dermatologica
1979;159:489–94.
19. Kumakiri M, Katoh N, Miura Y. Angioma serpiginosum. J Cutan Pathol 1980;7:410–21.
20. Chavaz P, Laugier P. Angiome serpigineux de Hutchinson: etude ultrastructurale. Ann Dermatol
Venereol 1981;108:429–36.
21. Polla LL, Tan OT, Garden JM, Parrish JA. Tunable pulsed dye laser for the treatment of benign cuta-
neous vascular ectasia. Dermatologica 1987;174:11–7.
22. Long CC, Lanigan SW. Treatment of angioma serpiginosum using a pulsed tunable dye laser. Br J
Dermatol 1997;136:631–2.
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136 Sangüeza and Requena / Pathology of Vascular Skin Lesions
2. INFANTILE HEMANGIOMAS
Infantile hemangiomas are the most common vascular proliferation in infancy. Tradi-
tionally this lesion has been classified among the benign neoplasms or hemangiomas
since it is created by a rapid proliferation of endothelial cells. However, their pattern of
behavior calls to mind a hyperplasia rather than a neoplasm, as the lesion characteristi-
cally has an initial rapid proliferative phase followed by a quiescent, nonproliferative (or
stable) phase, followed by involution. Although hemangiomas may be present at birth,
they usually delay appearance until the second week of life.
Erroneously, for many years infantile hemangiomas were designated as capillary,

cavernous, or mixed. In accordance with this classification, superficial hemangiomas
exhibited a “capillary” proliferation, deep hemangiomas exhibited “cavernous” configu-
rations, and a hemangioma that resided in the superficial and deep dermis exhibited
“mixed capillary and cavernous” components. Mulliken and Glowacki (1) affirmed that
all hemangiomas, at a given point in time, show a remarkably consistent architectural
pattern throughout the entire depth of the lesion. Thus the terms “capillary” and “cavern-
ous” are inappropriate both clinically and histopathologically. It is more appropriate to
designate bright red hemangiomas as superficial and those with normal overlying skin as
deep. Hemangiomas with both superficial and deep components appear bright red in their
exophytic portions which overlie the subcutaneous nodule.
C
LINICAL FEATURES
Superficial hemangiomas are found within the papillary dermis, whereas deep heman-
giomas are located in the reticular dermis and subcutaneous fat. Coloration is reflective
of the location of the lesion, with variance from a vivid crimson color in those of the
superficial dermis, to a bluish hue, overlain by normal skin, in those situated in the lower
dermis. Dilated veins or telangiectases may be seen on the surface of a deep hemangioma.
During infancy, it may be difficult to distinguish a hemangioma from a vascular
malformation (2). As distinctive features, hemangiomas are rarely visible at birth, but
they appear 2–3 wk thereafter and they grow rapidly during the first weeks of life.
Contrastingly, vascular malformations are usually evident at birth and enlarge commen-
surate with the child’s growth. As exceptions to this rule: (1) the noninvoluting congenital
hemangioma (3) is present at birth, grows proportionately with the child, and does not
regress; and (2) the congenital nonprogressive hemangioma (4) is present at birth, does
not show the typical postnatal proliferative phase, and remains stable.
Coloration is helpful in distinguishing a hemangioma from a vascular malformation.
The bright red color of a superficial hemangioma deepens during the first year of life,
whereas the hue of a vascular malformation persists unaltered. Palpation is also helpful.
Hemangiomas have a firm or rubbery consistency, whereas vascular malformations are
soft, easily compressible, masses. Unequivocal distinction is not always possible. Reex-

amination after a few weeks usually resolves the problem, since rapid growth during the
early weeks of life favors the diagnosis of hemangioma. As a practical matter, there is
rarely need for an immediate diagnosis and therapy. Imaging studies are also useful.
Noninvasive techniques, such as ultrasonography with Doppler studies, may disclose the
high-flow pattern of a hemangioma which is distinct from a solid tumor or vascular
malformation (5). With computed tomography, a proliferative hemangioma appears as
a well-circumscribed homogeneous lesion, whereas a vascular malformation shows
heterogeneous densities, sometimes with calcifications and multilocular cysts (6). Mag-
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Chapter 8 / Benign Neoplasms 137
netic resonance imaging (MRI) demonstrates well-circumscribed, densely lobulated
masses with an intermediate signal intensity on T
1
-weighted images and a moderately
hyperintense signal on T
2
-weighted images (7).
Infantile hemangiomas have a high prevalence. They affect 1–3% of all neonates (8,9)
and approx 10% of infants by the end of the first year of life (10,11). Evidence clearly
defines a higher incidence in premature infants, inversely related to the gestational age
at birth (12,13). The incidence of hemangioma is 10 times greater in children born of
women who had chorionic-villus sampling compared with children of women without
this maternal history (14). The incidence among twins denies hereditary factors (15). In
rare instances, however, hemangiomas are familial, and several kindreds reflect an
autosomal dominant pattern of inheritance (16).
At its inception, the lesion appears as a pink macule that enlarges to become a dome-
shaped, red to purple plaque with a smooth or lobulated surface. Although they may occur
anywhere on the skin, the head (Fig. 3) and neck (Fig. 4) are favorite locations, with the
trunk and limbs constituting sites of next frequency. Not uncommonly, hemangiomas
involve mucous membranes of the oral and genital regions. A solitary lesion is the rule;

however, 15–20% of involved infants manifest multiplicity. There may be visceral lesions
too (see below).
Infantile hemangiomas characteristically proceed through different stages: a growth
phase during the early years of life, a stable period, and then characteristically, sponta-
neous regression. Virtually, 100% of infantile hemangiomas undergo some degree of
Fig. 3. Infantile hemangioma involving the tip of the nose.
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138 Sangüeza and Requena / Pathology of Vascular Skin Lesions
Fig. 4. Ulcerated infantile hemangioma on the dorsum of the neck.
spontaneous regression (Fig. 5). It has been estimated that approx 30% of infantile
hemangiomas will have resolved by the third birthday, about 50% by the fifth, and about
70% by the seventh (17,18). If the hemangioma does not show signs of regression by the
time a child is 5 or 6 years of age, complete regression is unlikely. Lesions that exhibit
early changes of regression typically do so more rapidly with better cosmetic results (18).
The likelihood of spontaneous regression in infantile hemangiomas is not related to their
size, conventional anatomic location, number of aggregated lesions, or age of first
appearance. Nevertheless, unconventional hemangiomas of the tip of the nose, lip, and
parotid area are notably slow to involute (18). The appearance of white streaks of fibrosis
on the surface of a lesion is an early sign of regression. When the resolution is complete,
the affected area may resemble normal skin, but more commonly retains degrees of
atrophy, telangiectases, or redundant anetodermic skin.
Occasionally, infantile hemangiomas ulcerate during their proliferative phase with
resultant (1) permanent loss of tissue; (2) mutilation of the involved area; (3) recurrent
bleeding; or (4) secondary infection with septicemia (19). The location of the lesion may
introduce singular complications: (1) hemangiomas on the eyelids can impair vision and
result in amblyopia; (2) lesions of the nose, mouth, or upper airway may interfere with
feeding and/or respiration; and (3) hemangiomas on the ear may block the external
auditory canal sufficiently to impair hearing (20,21). In all these cases, directed treatment
may be required (22).
A consumptive coagulopathy (Kasabach-Merritt syndrome) is a serious complication

of large hemangiomas. This rare syndrome, first described in 1940 (23), consists of
thrombocytopenic purpura and chronic consumptive coagulopathy. Hemorrhage is a
consequence of platelet sequestration and the consumption of clotting factors within the
vascular spaces of the hemangioma (24–38). In general, this syndrome is associated with
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Chapter 8 / Benign Neoplasms 139
large hemangiomas localized on a limb or a portion of the trunk and proximal adjacent
limb. It has also been described in association with visceral angiomatosis, multiple glo-
mangiomas, and the blue rubber bleb nevus syndrome. Recent studies, however, have
confirmed that most cases of Kasabach-Merritt syndrome are not associated with com-
mon infantile hemangiomas, but with kaposiform hemagioendothelioma and tufted
angioma (39–41). Kasabach-Merritt syndrome occurs with greatest frequency during the
early weeks of life. Clinically, this coagulopathy should be suspected in children with
large hemangiomas who show pallor, petechiae or ecchymoses, bruisability, prolonged
bleeding from superficial abrasions or rapid changes in the size or appearance of a
hemangioma. In these cases, the hematologic evaluation should be prompt and should
include hematocrit, platelet count, prothrombin time, partial thromboplastin time,
fibrinogen level, and determination of fibrin split products (24). Although, in most cases
Kasabach-Merritt syndrome is self-limited and remits when the hemangioma begins to
involute, it could be fatal, with mortality figures cited from 20 to 30% (25,26). Consump-
tion coagulopathy and/or bleeding diathesis necessitate prompt therapy.
Extensive hemangiomas of the neck and face (PHACES syndrome) may be associated
with multiple anomalies, notably (1)
posterior fossa malformations; (2) hemangiomas of
the cervicofacial region; (3)
arterial anomalies; (4) cardiac anomalies; (5) ocular anoma-
lies; and (6)
sternal or abdominal clefting or ectopia cordis (42–48) (Figs. 6 and 7).
Hemangiomas of the lumbosacral region are markers for occult spinal malformations
and anomalies of the anorectal and urogenital regions (49,50). Imaging of the spine is

indicated for all patients with midline hemangiomas in this region.
Multiple cutaneous hemangiomas can coexist with visceral hemangiomas, an associa-
tion that has been variously termed diffuse neonatal hemangiomatosis, (51) disseminated
hemangiomatosis (52). disseminated eruptive hemangiomas (53), or miliary hemangio-
mas (54). (Figs. 8 and 9).Visceral lesions can involve the liver, gastrointestinal tract,
spleen, pancreas, adrenals, lungs, heart, skeletal muscle, salivary glands, kidney, bladder,
testes, thymus, thyroid, bone, meninges, brain, and eyes (51–60). Extensive visceral
involvement is associated with higher mortality during the early months of life, with
death resultant from congestive heart failure. Other complications include intestinal
bleeding, obstructive jaundice, convulsions, and central nervous system hemorrhage.
Fig. 5. Regression of infantile hemangioma (A) Infantile hemangioma involving the lateral aspect
of the elbow in a 6-mo-old boy. (B) The same lesion 2 yr later.
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140 Sangüeza and Requena / Pathology of Vascular Skin Lesions
Fig. 7. PHACES syndrome. Extensive hemangioma involving the neck, face, and parotid gland.
Fig. 6. PHACES syndrome. Extensive hemangioma involving the neck, face, and anterior chest.
Accordingly, infants with multiple cutaneous hemangiomas should be investigated by
ultrasound, X-ray, or MRI to rule out the possibility of visceral involvement. Multiple
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Chapter 8 / Benign Neoplasms 141
Fig. 9. Diffuse neonatal hemangiomatosis. Multiple infantile hemangiomas on the face, forearm,
and hand. The patient had extensive involvement of the lungs and liver by hemangiomas that
caused his demise.
Fig. 8. Diffuse neonatal hemangiomatosis. Multiple infantile hemangiomas scattered all over the
skin. The baby also had hemangiomas in the liver.
cutaneous hemangiomas, without signs or symptoms of visceral involvement, have been
termed benign neonatal hemangiomatosis (61,62) to reflect of the benign nature of the
disease. Spontaneous regression should be anticipated in mild cases of diffuse neonatal
hemangiomatosis (63) as well as in benign neonatal hemangiomatosis (61).
H

ISTOPATHOLOGIC FEATURES
The histopathologic composition of infantile hemangiomas varies with the age of the
lesion. Early hemangiomas are highly cellular and are characterized by plump endothe-
lial cells aligned to vascular spaces with small inconspicuous lumina (Fig. 10). At this
early stage, the vascular nature of the lesion may not be readily apparent. A moderate
number of normal mitotic figures may be present, and numerous mast cells may be seen
in the intervening stroma. It has been suggested that mast cells play a role in the produc-
tion of angiogenic factors that regulate the growth of the lesion (64,65). However, long-
standing hemangiomas have been found to have significantly more mast cells than
hemangiomas of recent origin; these findings obviate a role for mast cells in the early
proliferation of hemangiomas, indicating a contribution to the maturation of blood ves-
sels in the benign neoplasm (66). In some cases, capillary proliferation may involve
perineural spaces, but this should not be regarded as evidence of malignancy (67). As the
lesions mature, blood flow increases, the endothelium flattens, and the lumina of the
vessels enlarge and become more obvious (Fig. 11). During this interval the vessels
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142 Sangüeza and Requena / Pathology of Vascular Skin Lesions
present a “cavernous” appearance that can be misinterpreted as a venous malformation.
Regression is portrayed as progressive interstitial fibrosis and adipose metaplasia, a
process without known stimulus.
Congenital hemangiomas have a varied histopathologic appearance. Noninvoluting
congenital hemangiomas (3) feature lobular collections of small, thin-walled vessels
with large, often stellate, central lumina, separated by variable amounts of fibrous tissue
richly supplied with normal and abnormal veins and arteries. The lobules are predomi-
nantly composed of rounded or curved small, thin-walled channels lined by endothelial
cells and surrounded by one or more layers of pericytes. Several stellate vessels occupy
the center of the lobule. Most endothelial cells lining the intralobular vessels have abun-
dant cytoplasm and contain small, dark, hyperchromatic nuclei that protrude into the
lumen, thus creating a hobnail appearance. Many of the cells contain round, intracyto-
plasmic eosinophilic globules. The vascular elements between lobules are predominantly

elongated tortuous veins, many of which possess variable amounts of smooth muscle and
elastic tissue. Scattered vessels resemble lymphatic vessels, and accordingly, some pos-
sess valves.
Congenital nonprogressive hemangiomas (4) are highly cellular, with multiple well-
defined lobules of proliferating capillaries that anastomose with each other to form
ribbons within the dermis or subcutaneous tissue. In contrast to conventional infantile
Fig. 10. Histopathologic features of an early infantile hemangioma. (A) The entire thickness of the
dermis is involved by a cellular proliferation. (B) Higher magnification shows lobules of plump
endothelial cells with small inconspicuous lumina. (C) Still higher magnification shows vacuoles
and small channels as signs of primitive vascular differentiation.
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Chapter 8 / Benign Neoplasms 143
hemangioma, in which the tumor lobules are separated by normal tissue, bands of abnor-
mal, dense fibrous tissue or progressive sclerosis of capillary lobules separate the tumor
nodules of congenital nonprogressive hemangiomas (Fig. 12). Hemosiderin deposits and
small foci of dystrophic calcification are also present within both the capillary lobules and
the fibrous septi, as reminders that past hemorrhage or thrombosis play a role in the
evolution of these hemangiomas.
Immunohistochemical studies of hemangiomas demonstrate that the cells, which line
the lumina, express endothelial markers such as factor VIII-related antigen and CD34. A
few of the interstitial cells are positive for CD34 and α-smooth muscle actin, attesting to
their identity as pericytes. The remainder of the interstitial cells are negative for these
markers but strongly positive for factor XIIIa. Predominantly mitotic activity, as deter-
mined by the PC-10 antibody, is concentrated in the interstitial cells of areas with less
apparent vascularity and more prominent cellularity (65,68). These findings suggest that
hemangiomas are neoplasms derived from primitive cells with the capacity for differen-
tiation toward endothelial cells and pericytes (68). Hemangiomas in the proliferative
phase express high levels of angiogenic molecules such as basic fibroblast growth factor
(bFGF) and vascular endothelial growth factor/vascular permeability factor (VEGF/
VPF) (69), as well as high levels of the intercellular adhesion molecule (ICAM)-3 (70),

type IV collagenase (71), urokinase (71), and E-selectin (71). Interferon-β (IFN-β) is
Fig. 11. Histopathologic features of a mature hemangioma. (A) Dilated vascular structures with
congestive lumina are easily seen at different levels of the dermis. (B) The vascular structures
show thin walls and their lumina replete with erythrocytes.
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144 Sangüeza and Requena / Pathology of Vascular Skin Lesions
Fig. 12. Histopathologic features of congenital nonprogressive hemangioma. (A) Cellular heman-
gioma composed of multiple well-defined lobules of proliferating capillaries. (B) Bands of abnor-
mal, dense fibrous tissue separate the capillary lobules of congenital nonprogressive hemangiomas.
(C) The lobules are composed of aggregations of plump endothelial cells containing vascular
lumina inside.
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Chapter 8 / Benign Neoplasms 145
notably absent (69). During the regression phase, apoptosis is more in evidence (72).
Urinary levels of basic fibroblast growth factor (bFGF) are elevated considerably in
infants with hemangiomas, and this offers a potential means of monitoring the efficacy
of treatment (73).
Recent immunohistochemical studies have demonstrated that the endothelial cells of
infantile hemangiomas express immunoreactivity for the erythrocyte-type glucose trans-
porter protein GLUT-1 (74,75) (Fig. 13) and the placenta-associated antigens Fc RII,
Lewis Y antigen (LeY), and merosin (74). Their presence supplies evidence that infantile
hemangiomas and human placenta share a unique microvascular phenotype. On the other
hand, immunohistochemical studies have failed to demonstrate placental alkaline phos-
phatase and human placental lactogen in infantile hemangiomas. These findings do not
support the notion that placental trophoblasts play a role in the development of infantile
hemangiomas (76). Immunohistochemical studies for GLUT-1 in noninvoluting congeni-
tal hemangioma (3) and congenital nonprogressive hemangioma (4) have yielded negative
results. The summarized evidence suggests that congenital hemangiomas are histopatho-
logically and immunophenotypically distinct from classical infantile hemangiomas.
By ultrastructural studies, hemangiomas exhibit small vascular spaces lined by a

single continuous layer of endothelial cells surrounded by a basement membrane and
pericytes (77,78). Intracytoplasmic vacuoles are present and are interpreted as an expression
of the early stages in lumen formation (79). Weibel-Palade bodies are either poorly formed
or unrecognizable in the earlier lesions. Crystaloid inclusions of uncertain nature have
been observed in the immature endothelial cells (80,81). The vascular spaces within
hemangiomas may have ultrastructural features of capillaries, venules, and arterioles (82).
T
REATMENT
The treatment of infantile hemangiomas has to be individualized for each patient. Most
lesions regress spontaneously during the first years of life, and the best cosmetic results
are often achieved with expectant management. When hemangiomas interfere with
important structures or functions, active treatment is required. Options include
intralesional or systemic corticosteroids, sclerosing injections, cryotherapy, laser therapy,
compression and embolization, surgical excision, and radiotherapy (83–91). The proper
alternative is governed by the location, size, and phase of development of the hemangioma
as well as personal experience in the management of each therapy, and knowledge of
the advantages and disadvantages of the available therapeutic options.
In most children with Kasabach-Merritt syndrome, surgery is not generally an option
because of the precarious hematologic status of the patient and the large size of the
lesions, although it has been performed successfully in some cases (25,27,28). In some
patients, a course of prednisone therapy at a dosage of 2–4 mg/kg/d has elevated the
platelet count and caused shrinkage of the hemangioma (24,29–31). Corticosteroids
increase the survival time of platelets, reduce the vascular mass, and restore the integrity
of the clotting system. Radiotherapy has been administered to patients with Kasabach-
Merritt syndrome, but its potential long-term negative sequelae have lessened the
acceptability or this therapy (32,33). Additional therapeutic options include INF-α-2a
(34) and pentoxifylline (35). Administration of heparin may be required if thrombosis
and
bleeding occur. It is recommended at a dosage of 100 U/kg every 4 h until bleeding ceases,
the platelet count is stable, and the coagulation defect is under control (26). Hepariniza-

tion should be followed by replacement of platelet concentrates, fresh frozen plasma, and
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146 Sangüeza and Requena / Pathology of Vascular Skin Lesions
Fig. 13. An early infantile hemangioma stained with hematoxylin-eosin and GLUT-1. (A) Low
power shows a cellular proliferation involving the entire thickness of the dermis. (B) Higher
magnification demonstrates that some small vascular lumina are also seen in the cellular
proliferation. (C) Still higher magnification demonstrates that the lumina are lined by plump
endothelial cells. (D) A section of the same infantile hemangioma immunohistochemically stained
for GLUT-1. (E) Higher magnification demonstrates GLUT-1 immunoreactivity of most endothe-
lial cells lining vascular lumina.
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