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Verrucous hemangioma and histopathological differential diagnosis with angiokeratoma circumscriptum neviforme

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Kenselyn Oppermann
Kenselyn Oppermann
Kenselyn Oppermann
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Ana Boff
Ana Boff
Renan Rangel Bonamigo at Universidade Federal do Rio Grande do Sul
Renan Rangel Bonamigo
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Abstract

Verrucous hemangioma is a rare vascular skin disorder with an immune profile similar to vascular neoplasms, but with behavior and evolution of vascular malformations. Its main differential diagnosis is angiokeratoma circumscriptum neviforme, with an almost indistinguishable clinical presentation because both diseases appear as erythematous patches that evolve to violaceous plaques, becoming scaly and even verrucous, most commonly affecting the lower limbs. Histopathology is crucial for the correct diagnosis: while in angiokeratoma the vascular alterations are limited to the papillary dermis, verrucous hemangioma extends deep into the dermis, reaching the subcutaneous tissue.
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An Overview About Oxidation in Clinical Practice of Skin Aging 712
dermAtopAthology
Verrucous hemangioma and histopathological differential diagnosis with
angiokeratoma circumscriptum neviforme*
Kenselyn Oppermann1, Ana Letícia Boff2, Renan Rangel Bonamigo1,3
DOI: http://dx.doi.org/10.1590/abd1806-4841.20187259
Abstract: Verrucous hemangioma is a rare vascular skin disorder with an immune profile similar to vascular neoplasms, but
with behavior and evolution of vascular malformations. Its main differential diagnosis is angiokeratoma circumscriptum
neviforme, with an almost indistinguishable clinical presentation because both diseases appear as erythematous patches that
evolve to violaceous plaques, becoming scaly and even verrucous, most commonly affecting the lower limbs. Histopathology
is crucial for the correct diagnosis: while in angiokeratoma the vascular alterations are limited to the papillary dermis, verru-
cous hemangioma extends deep into the dermis, reaching the subcutaneous tissue.
Keywords: Angiokeratoma; Hemangioma; Skin diseases, vascular
s
CASE REPORT
Female patient, phototype IV, four years of age, with a his-
tory of a reddish irregular patch on the right lumbosacral region
that appeared in the first year of life, with rapid and progressive
increase, evolving to a hyperkeratotic, verrucous plaque affecting
the entire right lower limb, including the plantar region. The lesion
was asymptomatic, and there was no report of local trauma or fam-
ily history.
On detailed physical examination, the lesion showed a li-
near pattern and morphological differences according to the topo-
712
Received 15 May 2017.
Accepted 04 February 2018.
* Work conducted at the Public Health Dermatology Outpatient Clinic of Porto Alegre, Rio Grande do Sul State Health Department, Porto Alegre (RS), Brazil.
Financial support: None.
Conflict of interest: None.
1 Dermatology Department and Public Health Dermatology Outpatient Clinic, Porto Alegre, Rio Grande do Sul State Health Department, Porto Alegre (RS),
Brazil.
2 Pathology Department, Hospital Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS), Brazil.
3 Dermatology Department, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre (RS), Brazil.
Mailing address:
Kenselyn Oppermann
E-mail: kenselyn@gmail.com
©2018 by Anais Brasileiros de Dermatologia
graphy: it was more erythematous-violaceous on the gluteal region,
predominantly scaly on the posterior aspect of the leg, extending to
the ipsilateral plantar region, where it appeared as an erythematous
patch (Figures 1, 2, and 3). Comparative measurements of the lower
limbs showed no discrepancy; X-rays of the lower limbs and electro-
cardiogram were normal.
Anatomical pathological examination showed mild hy-
perkeratosis, prominent papillomatosis, and proliferation of small
and medium-caliber blood vessels located in the papillary dermis,
An Bras Dermatol. 2018;93(5):712-5.
FIgure 1: Ex-
tensive lesion
with erythema-
tous-violaceous
squamous
plaques with a
linear pattern
FIgure 3: Detail
of keratotic le-
sion on posterior
leg
FIgure 2: Detail
of erythema-
tous-violaceous
lesion on
lumbosacral and
gluteal regions
and posterior
thigh
FIgure 4: Overall appearance on histopathology. Mild hyperkerato-
sis and acanthosis; papillomatosis; vascular proliferation, predomi-
nantly in the papillary dermis (Hematoxylin & eosin, x50)
An Bras Dermatol. 2018;93(5):712-5.
extending to the subcutaneous tissue (Figures 4 and 5). Combined
clinical and histopathological findings determined the diagnosis as
verrucous hemangioma (VH).
DISCUSSION
VH is a rare congenital vascular anomaly with a clinical
presentation very similar to that of angiokeratoma circumstriptum
neviforme (ACN). The International Society for the Study of Vas-
cular Anomalies (ISSVA) stratifies vascular anomalies into vascular
tumors and vascular malformations. Vascular tumors, such as in-
Verrucous hemangioma and histopathological differential diagnosis with angiokeratoma circumscriptum neviforme 713
714 Oppermann K, Boff AL, Bonamigo RR
An Bras Dermatol. 2018;93(5):712-5.
FIgure 5: Fundamental detail on histopathology. Proliferation of
small vessels also in the subcutaneous tissue, characteristic of ver-
rucous hemangioma (Hematoxylin & eosin, x200)
fantile hemangiomas, result from exacerbated cell proliferation, are
more prevalent in females, tend to regress with the child’s growth,
and present positive immunohistochemistry for WT1 (Wilms tumor
1 protein) and GLUT1 (glucose transporter-1 protein).1 On the other
hand, vascular malformations consist of errors in vessel morpho-
genesis, with equal male/female prevalence, that grow proportion-
ally with the child, and that do not display involution or positive
IHC for WT1 or GLUT1.1
Despite important efforts to standardize the nomenclature
for vascular anomalies, the case reported here illustrates the diffi-
culty in classifying these disorders. Some authors, like Imperial and
Helwig, consider VH a malformation involving the subcutaneous
tissue, with reactive acanthosis and epidermal hyperkeratosis;2
however, other authors consider it a true hemangioma (tumor),
since its present positivity for WT1 and GLUT1.3 The ISSVA classi-
fication of 2014 includes VH — as well as its principal differential
diagnosis, ACN — in the disorders yet not classified, since the clini-
cal-pathological characteristics are still not totally clear.1
The clinical presentation of VH and ACN include erythem-
atous patches that evolve to squamous and even verrucous plaques,
most often affecting the lower limbs.4,5 Given the clinical similarity,
anatomical pathological examination is imperative for diagnostic
confirmation. In ACN the epidermal findings of acanthosis with hy-
perkeratosis — often even hypergranulosis — are very evident and
charT 1: Differences between verrucous hemangioma and
angiokeratoma circumscriptum neviforme
VH ACN
Age at onset At birth or in early
infancy
At birth or in early
infancy
Sex No predilection, or
male predominance?
Females (3:1)
Clinical
presentation
Violaceous
hyperkeratotic
plaques on lower
limbs
Violaceous
hyperkeratotic
plaques on lower
limbs
Histopathology Involvement of the
subcutaneous tissue
Involvement of the
papillary dermis
IHC Positive to GLUT1
and WT1
No reports of
positivity
Evolution Progression
accompanies child’s
growth
No reliable data
Management Laser (deeper) Cryotherapy,
electrocoagulation,
curettage, laser,
surgery
the vascular alterations are limited to the papillary dermis, whereas
in VH the papillomatosis is a predominant feature, with vascular
proliferation, and besides accompanying the papillomatosis in the
papillary dermis, the vessels extend to the deep dermis and subcu-
taneous tissue. Chart 1 summarizes the differences between the two
disease entities.
Another especially important complementary test is the
scanogram, which measures the limbs comparatively. In the pres-
ence of asymmetry, Klippel-Trenaunay syndrome (KTS) should be
remembered. The syndrome is characterized by the triad of Port
wine stain, venous and lymphatic malformations, and hypertrophy
of soft tissues in the affected area. There are some reports of associ-
ation between ACN and KTS.5
Since VH lesions do not regress, but expand as the child
grows, treatment becomes challenging. Combined therapy with
surgery and laser is considered the first choice, and alternatives in-
clude cryotherapy and electrocoagulation.6 In more extensive cases,
in which surgery becomes unfeasible, sirolimus can be an interest-
ing option.7 q
VH: verrucous hemangioma; ACN: angiokeratoma circumscriptum neviforme; IHC:
immunohistochemistry
Verrucous hemangioma and histopathological differential diagnosis with angiokeratoma circumscriptum neviforme 715
REFERENCES
1. Wassef M, Blei F, Adams D, Alomari A, Baselga E, Berenstein A, et al. Vascular
Anomalies Classification: Recommendations from the International Society for the
Study of Vascular Anomalies. Pediatrics. 2015;136:e203-14.
2. Imperial R, Helwig EB. Verrucous hemangioma. A clinicopathologic study of 21
cases. Arch Dermatol. 1967;96:247-53.
3. Knöpfel N, Hoeger PH. Hemangioma verrucoso o malformación venosa
verrucosa? Hacia una clasificación asentada em el estudio genético. Actas
Dermosifiliogr. 2016;107:427-8.
4. Ghosh SK, Bandyopadhyay D, Ghoshal L, Haldar S. Angiokeratoma circumscriptum
naeviforme: A case report of a rare disease. Dermatol Online J. 2011;17:11.
5. Wankhade V, Singh R, Sadhwani V, Kodate P, Disawal A. Angiokeratoma
circumscriptum naeviforme with soft tissue hypertrophy and deep venous
malformation: A variant of Klippel Trenaunay syndrome? Indian Dermatol Online
J. 2014;5:S109-12.
6. Yang CH, Ohara K. Successful surgical treatment of verrucous hemangioma: a
combined approach. Dermatol Surg. 2002;28:913-19.
7. Hammill AM, Wentzel M, Gupta A, Nelson S, Lucky A, Elluru R, et al. Sirolimus
for the Treatment of Complicated Vascular Anomalies in Children. Pediatr Blood
Cancer. 2011;57:1018-24.
How to cite this article: Oppermann K, Boff AL, Bonamigo RR. Verrucous hemangioma and histopathological differential diagnosis with
angiokeratoma circumscriptum neviforme. An Bras Dermatol. 2018;93(5):712-5.
An Bras Dermatol. 2018;93(5):712-5.
AUTHORS’CONTRIBUTIONS
Kenselyn Oppermann 0000-0003-0519-2868
Preparation and writing of the manuscript, Collecting, analysis and interpretation of
data, Effective participation in research orientation, Critical review of the literature
Ana Letícia Boff 0000-0002-5207-0567
Effective participation in research orientation
Renan Rangel Bonamigo 0000-0003-4792-8466
Approval of the final version of the manuscript, Effective participation in research orien-
tation, Intellectual participation in propaedeutic and/or therapeutic conduct of studied
cases, Critical review of the literature, Critical review of the manuscript
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... Verrucous venocapillary malformation (VVM), formerly known as verrucous hemangioma, is characterized by well-demarcated, single or multiple, dark red/purple or black verrucous plaques and nodules which may show hyperkeratinization, thickening, darkening and bleeding [1,2]. VVM usually appears at birth or during early childhood [2]. On the other hand, angiokeratomas are welldemarcated vascular lesions which are characterized histopathologically by superficial vascular ectasia accompanied by hyperkeratosis [3]. ...
... VVM, also known as verrucous hemangioma, is a rare congenital vascular malformation which is usually localized to the lower extremity, unilaterally [2]. Even though, VVM has an immune profile analogous to the vascular proliferations; it exhibits histopathological features, clinical behavior and evolution pattern of vascular malformations [2,3]. ...
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... 30,31 Penegakan diagnosis VH dilakukan terutama dengan pemeriksaan histopatologi. 32,33 Menurut literatur, gambaran histopatologi VH dengan pewarnaan HE menunjukkan gambaran hiperkeratosis, akantosis epidermis yang bervariasi dan telangiektasis papiler yang menutupi hemangioma kavernosa atau kapiler profunda. 22 Gambaran histopatologi yang merupakan karakteristik VH adalah epidermis hiperplasia reaktif yang ditandai dengan akantosis irregular, hiperkeratosis dan papilomatosis. ...
... 2,32 Pada ACN ditemukan akantosis, hiperkeratosis bahkan hipergranulosis pada epidermis, perubahan vaskular terbatas pada dermis papiler, sedangkan pada VH papilomatosis merupakan gambaran utama disertai proliferasi vaskular dalam papila dermis yang meluas ke dermis dalam dan jaringan subkutan. 13,32 Pada kasus ini, hasil pemeriksaan histopatologi menyokong diagnosis VH. Pengambilan biopsi yang dalam hingga jaringan subkutan merupakan langkah diagnostik yang penting dan perlu ditekankan, karena pada biopsi superfisial gambaran lesi VH cenderung serupa dengan ACN. ...
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  • Dec 2011
  • PEDIATR BLOOD CANCER
Vascular anomalies comprise a diverse group of diagnoses. While infantile hemangiomas are common, the majority of these conditions are quite rare and have not been widely studied. Some of these lesions, though benign, can impair vital structures, be deforming, or even become life-threatening. Vascular tumors such as kaposiform hemangioendotheliomas (KHE) and complicated vascular malformations have proven particularly difficult to treat. Here we retrospectively evaluate a series of six patients with complicated, life-threatening vascular anomalies who were treated with the mTOR inhibitor sirolimus for compassionate use at two centers after failing multiple other therapies. These patients showed significant improvement in clinical status with tolerable side effects. Sirolimus appears to be effective and safe in patients with life-threatening vascular anomalies and represents an important tool in treating these diseases. These findings are currently being further evaluated in a Phase II safety and efficacy trial.
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Successful Surgical Treatment of Verrucous Hemangioma: A Combined Approach
Article
  • Nov 2002
Verrucous hemangioma, also known as angiokeratoma circumscriptum naeviforme, is a rare congenital vascular abnormality. Episodes of bleeding and infection following trauma or scratching are frequent. Superficial ablative therapies using laser, cryotherapy, and electrocautery are always followed by recurrence. To report the clinical and histopathologic characteristics and treatment results of verrucous hemangioma. This study included 23 patients with verrucous hemangioma treated by en toto surgical excision in combination with laser therapy. Palpation, inspection, computed tomography (CT), or magnetic resonance imaging (MRI) was performed to delineate surgical margins. The clinical presentation of verrucous hemangioma ranged from a small solitary verrucous plaque or cluster of lesions with unilateral limb involvement to Klippel-Trenaunay syndrome with bone hypertrophy. Histologically all specimens revealed the existence of hemangioma-like components in the subcutaneous tissue and dilated subepidermal blood cysts. The 14 patients presenting with small, localized lesions were cured by one session of surgery without recurrence, while the 9 patients with wider and more extensive lesions required combination therapy in several stages for optimal results. Surgical excision in combination with laser therapy is the preferred treatment for verrucous hemangioma because the crucial pathologic change is concentrated in the subcutaneous tissue. The use of clinical inspection, palpation, and imaging studies before surgery is helpful in delineating the underlying mass.
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Hemangioma verrucoso o malformación venosa verrucosa? Hacia una clasificación asentada em el estudio genético
  • Jan 2016
  • 427
  • Knöpfel N
Knöpfel N, Hoeger PH. Hemangioma verrucoso o malformación venosa verrucosa? Hacia una clasificación asentada em el estudio genético. Actas Dermosifiliogr. 2016;107:427-8.