Tumors of vascular origin

Middle-aged adults

Slight female predominance

Predilection for the head and neck, extremities (particularly fingers), and trunk

Occasionally on mucosal surfaces

Slowly growing, solitary reddish, violaceous or bluish papule or nodule

Less than 2 cm in diameter

History of previous trauma in less than 5%

Multiple lesions and eruptive occurrence exceptional (very rarely associated with interferon treatment)

Sometimes intravascular

Simple excision is curative

Local recurrence rare; more common in cases associated with a preexistent vascular lesion

Multiple recurrences exceptional, possibly linked to microthrombus formation due to associated coagulopathy

Three different types occur

• Primary: within a preexistent normal vessel, usually a vein

• Secondary or mixed: in the background of a preexistent vascular lesion (e.g., malformation or tumor)

• Extravascular: usually in an organizing hematoma

Well-circumscribed and in most cases intravascular proliferation in the deep dermis and/or subcutis

Arborizing and interconnecting intraluminal projections, forming a meshwork of cleftlike spaces with cores composed of fibrin, hypocellular collagen, and capillaries

• Lined by a single layer of endothelial cells

  • Plump or swollen

  • Mild nuclear pleomorphism

  • Occasional mitoses

• Attached to the vessel wall or lying freely within the lumina

Remnants of a preexistent thrombus in different stages of organization often seen

Well-differentiated angiosarcoma

Lymphangioma

Nearly equal sex distribution (F:M = 1.3 : 1)

All age groups can be affected, from infancy to elderly, median age 60 years

Wide site distribution, with propensity for limbs, face, or trunk

Associated conditions include

• Systemic infections (previous subacute bacterial endocarditis and tuberculosis)

• Malignancies (glioblastoma multiforme, myelodysplastic syndrome, angiosarcoma)

• Vasculitides and vasculopathies (leukocytoclastic vasculitis, atherosclerosis, dermal amyloid angiopathy)

• Iatrogenic arteriovenous fistulas

• Autoimmune diseases (systemic lupus erythematosus with antiphospholipid syndrome, rheumatoid arthritis, polymyalgia rheumatica, sarcoidosis)

• Cryoproteinemia and cryoglobulinemia

• Iatrogenic immunosuppression

• Valvular cardiac disease

• Alcoholic liver cirrhosis

• Renal and liver failure

• Liver transplantation

• Graft versus host disease

Heterogeneous clinical presentation

Localized to a particular region (more common) or generalized

Annular or reticular macules (livedo-like pattern), erythematous or violaceous papules, purpuric or indurated plaques

Subsequent development of blisters, ulcers, and necrosis

No specific treatment available

The lesions generally resolve after eliminating the underlying cause

Recurrence possible

Poorly demarcated proliferation, predominantly but not exclusively within the dermis

Extravascular and/or intravascular proliferation of endothelial cells with solid growth or formation of capillary-type blood vessels with well-defined lumina

• Capillaries are generally closely packed

• No significant atypia of endothelial cells

• No multilayering

Layer of pericytes surrounding vascular channels always present

Additional features

• Intraluminal fibrin thrombi frequent with features suggesting organization

• Hyaline eosinophilic thrombi in cases related to cryoglobulinemia or with antiphospholipid syndrome

• Infrequent reactive fasciitis-like spindle cell proliferation

• Inflammatory cells rare

• Hemosiderin deposition

• Extravasation of erythrocytes

• Very rarely dermal fibrosis

Intravascular lymphoma

Intravascular histiocytosis

Glomeruloid hemangioma

Tufted angioma

Present in about 3% of patients with POEMS syndrome

No sex predisposition

Very rare cases reported in patients without POEMS syndrome

Early lesions consist of red/erythematous macules

Established lesions consist of multiple dome-shaped, firm, nontender, red or violaceous papules or nodules with smooth surface varying in size from a few millimeters to a few centimeters

Predilection for trunk and proximal limbs

Extracutaneous locations exceedingly rare (retroperitoneal fatty tissue and uterus)

Can be a presenting feature of the POEMS syndrome, preceding the development of other symptoms by years, necessitating long-term follow-up

Exceptional cases, especially those presenting as a solitary lesion, might not be associated with POEMS syndrome

Patients with POEMS syndrome commonly associated with a progressive and disabling clinical course and poor prognosis

Usually localized within the upper and middermis

Numerous endothelial-lined dilated spaces, possibly veins, containing organoid proliferations of capillary-sized blood vessels and sinusoid-like spaces resembling capillary loops of renal glomeruli

• Lined by a single layer of bland endothelial cells

• Capillary loops surrounded by pericytes

Plump “stromal” endothelial cells interspersed between capillary loops, containing intracytoplasmic vacuoles and globules

• Clear cytoplasmic vacuoles

• Eosinophilic globules

  • Periodic acid–Schiff positive, diastase resistant

  • Enlarged secondary lysosomes (thanatosomes), containing accumulated polytypic immunoglobulins and other proteinaceous material

Histological features of cherry hemangioma and cirsoid aneurysm occasionally present in the same or in different biopsy specimens in patients with POEMS syndrome

Papillary hemangioma

Intravascular pyogenic granuloma

Intravascular papillary endothelial hyperplasia (Masson tumor)

Tufted angioma

Male predominance (M:F = 7 : 5)

Wide age distribution (from 2 to 77 years), median age 57 years

All lesions described in the head and neck area, with predilection for the face

Solitary skin-colored to bluish papule or nodule

Size from 0.3 to 1.5 cm (median size 1.1 cm)

Complete excision curative

Local recurrence exceptional

Well-circumscribed, dermal, vascular proliferation with occasional involvement of the subcutaneous tissue

Dilated vascular spaces, usually veins, containing papillary projections composed of branching multilayered cores

Capillaries within papillary projections

• Limited in numbers

• Not arranged in an organoid or glomeruloid pattern

• Lined by a single layer of normal endothelial cells

• Erythrocytes within the lumina

• Aggregates of platelets occasionally seen within the lumina

Pericytes, usually arranged in several layers

Fibrillary and hyaline collagen in the stroma

Endothelial cells at luminal surfaces of papillae

• Typically contain numerous hyaline globules in their cytoplasm indenting the nucleus

• Hyaline globules represent giant lysosomes and are filled with cellular debris and fat vacuoles (thanatosomes)

• Endothelial cells tend to detach from the surface

Collagen IV delineates thick, basement membrane–like matrix surrounding pericytes and outlines papillary architecture of intravascular proliferation

In glomeruloid hemangioma, in contrast, the layer of basement membrane–like material is generally thin, enabling separation of the two entities

Glomeruloid hemangioma

Intravascular pyogenic granuloma

Intravascular papillary endothelial hyperplasia (Masson tumor)

Port wine stain

• Prevalence from 0.3% to 0.5% of newborns

• No gender predisposition

• Less common in African Americans and Asians

Salmon patch

• As much as 70% of newborns can be affected

• Differences according to skin color and ethnic groups

• Highest prevalence in whites (Caucasians)

• More common in girls

• Increased frequency in infants born to mothers older than 30 years and with no previous pregnancies

Port wine stain

• Typically present at birth

• The majority of cases sporadic

• Familial occurrence rare, with autosomal-dominant mode of inheritance and important role of RASA1 gene mutation(s) in their pathogenesis, implicating the RAS/ERK pathway

• Acquired variants rare, related to trauma (Fegeler syndrome), drugs (oral contraceptives, isotretinoin, simvastatin, metformin), chronic sun exposure, hormonal changes (pregnancy, puberty), frostbite injuries, herpes zoster infection

• Localized, unilateral or segmental growth, rarely more widespread

• Most commonly on the face, along the trigeminal nerve distribution following the ophthalmic branch or V1 (upper eyelid, forehead), the maxillary branch or V2 (upper lip, cheek, lower eyelid), and the mandibular branch or V3

• Early lesions consist of well-defined, persistent macular erythema

• Over time, thickening of the lesion with verrucous appearance, irregular surface, and formation of nodule(s), with change of the color from pink to dark purple

• Size and distribution of lesions do not change with increasing age

• Associated syndromes

  • Sturge–Weber syndrome

    • Facial port wine stain, ipsilateral leptomeningeal vascular anomalies, and/or choroidal vascular lesions with glaucoma

    • Highest risk for neuroocular symptoms when the port wine stain involves dermatome V1

  • Klippel–Trénaunay syndrome

    • Port wine stain, varicose veins with or without venous malformations, and bony/soft tissue hyperplasia

  • Cobb syndrome

    • Port wine stain overlying an underlying spinal cord malformation in the middle of the back

  • Phakomatosis pigmentovascularis

    • Coexistence of cutaneous vascular malformation, most often port wine stain and ocular or dermal melanocytosis/melanocytic nevus

  • Newly reported syndrome (CLAPO)

    • Port wine stain of the lower lip (C, capillary), lymphatic malformation of face/neck (L), asymmetry of face and limbs (A), and partial/generalized (P) overgrowth (O)

• Other associated conditions

  • Oral mucosa vascular malformation and multiple lipomas

  • Intraoral hemangioma

  • Linear epidermal nevus and optic pathway glioma

  • Acoustic neuroma in the cerebellopontine angle

  • Congenital and acquired port wine stain in a single patient

  • Familial port wine stain and multiple cherry angiomas occurring at young age

  • Familial association of port wine stain and arteriovenous malformations appear to be linked to mutation in RASA1 gene

  • Pneumosinus dilatans

  • Microcystic lymphatic malformation and Noonan syndrome

  • Cutis marmorata telangiectatica congenita

  • Nevus sebaceous

  • Café au lait spots

  • Turner syndrome with ring X chromosome

• Lesions developing within port wine stain include pyogenic granuloma, arteriovenous malformation, tufted angioma, spongiotic dermatitis (eczema) with or without impetiginization, folliculosebaceous cystic hamartoma, Becker nevus, basal cell carcinoma, squamous cell carcinoma

Salmon patch

• Generally present at birth

• Familial occurrence rare; mode of inheritance autosomal dominant in such cases, possibly linked to RASA1 gene mutation on locus 5q13~22

• Most common sites include nape of the neck, eyelids, and glabella

• More than one particular site can be affected

• Irregular pink to reddish macules

• Blanch under pressure

• Becomes more visible by crying, breath holding, fever, and changes in the environmental temperature

• Associated syndromes rare and include Beckwith–Wiedemann syndrome, macrocephaly capillary malformation syndrome, and Nova syndrome

Port wine stain

• Does not regress and characteristically grows proportionally with child's growth

Salmon patch

• Generally regresses within first years of life

• About 50% of the lesions on the nape of the neck and sacral area, as well as minor proportion of glabellar lesions, show persistence

Early treatment of port wine stain is of paramount importance to obtain good cosmetic results

Treatment options predominantly include laser therapy

Superficial and deep, dilated capillaries and postcapillary venules

Histological changes minimal at birth

Subsequent development of ectasis with possible thickening of vessel walls

Formation of nodules within port wine stain has been linked to development of arteriovenous malformation(s) in the background of preexistent vascular lesion

Clinical presentation typical with generally no relevant differential diagnosis

Equal gender distribution

The majority of lesions already present at birth or shortly thereafter

Late onset possible, but rare

Sporadic presentation predominates

Familial occurrence exceptional (autosomal-dominant inheritance with incomplete penetrance)

Fixed reticular erythema, from deep violet to red

Thin, coarse or broad streaks, forming train track–like pattern or mosaic distribution

Pallor of skin between vascular network, giving the lesion a mottled appearance

Lesions do not disappear after warming

Ulceration, especially over the elbows and knees

Atrophy of skin and subcutaneous tissue in the affected area

Predilection for limbs, followed by trunk and face

Mucosal involvement distinctly uncommon

Localized variant (more common, about 60%)

• Tends to remain unilateral

• Sharply demarcated

• No crossing of the midline

• Predilection for extremities and trunk

Generalized variant (less common, about 40%)

• Does not involve entire body surface

• In addition to extremities and trunk, scalp and face are usually affected

• Involvement of palms, soles, and mucous membranes rare

Extent of cutaneous involvement does not predict the possibility or severity of other related abnormalities

Associated abnormalities present in more than half of the patients, including

• Body asymmetry, most common (limb hyperplasia or hypoplasia, occasional facial asymmetry, atrophy of the overlying skin frequent)

• Vascular anomalies (port wine stain, angiokeratoma[s], hemangioma of infancy, diffuse dermal angiomatosis)

• Skeletal abnormalities (syndactyly, tendinitis stenosans, hip dysplasia, clubfoot, cleft palate, scoliosis, skull asymmetry, scaphoid scapula, micrognathia, osteoporosis)

• Neurological disorders (more commonly part of macrocephaly cutis marmorata telangiectatica congenita syndrome, recently reclassified as macrocephaly capillary malformation, which has been regarded as a distinct entity not related to cutis marmorata telangiectatica congenita)

• Ocular malformations (glaucoma, strabismus, granular retinal pigmentation, small optic disc, optic nerve atrophy)

Associated conditions include dermal melanocytosis (Mongolian spot), café au lait macules, congenital melanocytic nevi, neonatal lupus erythematosus, chronic autoimmune urticaria, hypothyroidism, hypospadias, cardiovascular abnormalities, renal cysts, duplication of renal collecting system, formation of fistulas between gastrointestinal and urogenital tract, absent clitoris, anal atresia, Kartagener syndrome, hemophagocytic lymphohistiocytosis, myelodysplasia

Adams–Oliver syndrome combines cutis marmorata telangiectatica congenita with aplasia cutis congenita, transverse limb defects, and various other malformations

Some of the associated abnormalities and conditions likely to be coincidental

Recently proposed diagnostic criteria (three major and two minor required)

• Major

  • Congenital reticulate (marmorated) erythema

  • Absence of venectasia

  • Unresponsiveness to local warming

• Minor

  • Fading of erythema within 2 years

  • Telangiectasia

  • Ulceration

  • Atrophy

  • Port wine stain outside the lesional area

Cutaneous lesions usually self-limiting

Significant improvement with maturity

Progressive fading of the lesion, usually within the first 2 years

Complete disappearance possible, but rare

Persistence of the lesions into adulthood not unusual

No treatment generally necessary

Dilated preexisting capillaries and veins in the superficial dermis

Swelling of endothelial cells occasionally seen

Increase in the number of dermal capillaries and veins rare

Physiological cutis marmorata

Persistent cutis marmorata, also associated with genetic syndromes

Livedo racemosa

Diffuse phlebectasia (Bockenheimer syndrome)

Klippel–Trénaunay syndrome

Neonatal lupus erythematosus

Frequent in normal population (10%–15% of healthy individuals)

More than five lesions in otherwise healthy individuals not uncommon

All age groups can be affected, including children (two peaks in childhood and early middle age)

Predilection for the face, upper chest, neck, shoulders, back of the hands, forearms, and ears

Size from 0.5 to 1 cm

Bright red macule or slightly elevated papule consisting of a central arteriole with radiating thin-walled vessels

Compression of arteriole results in blanching and obliteration of the lesion

Rapid gradual refilling of the lesion from the central arteriole upon release of pressure

Numerous spider angiomas, especially on trunk and face, may signify association with an underlying chronic liver disorder (e.g., alcohol-related liver cirrhosis)

Eruptive or multiple lesions reported in pregnancy, thyrotoxicosis, hyperviscosity syndrome, in patients on oral contraceptive drugs, after discontinuation of oral contraceptives, in rheumatoid arthritis patients receiving estrogen therapy

In children, multiple spider angiomas are not a reliable marker of associated liver disease

No treatment generally required

Treatment options include pulsed dye laser, electrocoagulation

Dilatation of preexisting blood vessels in the superficial and middermis

Cherry angioma

Angioma serpiginosum

Angiokeratoma

Disseminated essential telangiectasia

Strong female predominance (about 90%)

The majority of lesions develop in the first two decades of life

Grouped red puncta on a macular, red to violaceous background

Central clearance with formation of new, occasionally papular, irregular lesions at the periphery, giving the lesion a serpiginous appearance

Lesions are nonblanchable

Asymptomatic, slowly progressive, and chronic

Wide anatomical distribution, predilection for lower extremities

Palms, soles, and mucosal surfaces generally spared, although involvement of the soles reported in exceptional cases

Rare presentations include linear distribution, distribution along Blaschko lines, symmetrical distribution, and more widespread or generalized

Involvement of the eye and spinal nerves exceptionally reported

Sporadic presentation in the majority of cases

Familial presentation extremely rare

• Autosomal-dominant and X-linked dominant pattern of inheritance reported

• Development of angioma serpiginosum has been linked to deletion of PORCN gene on chromosome X in one family

No treatment usually necessary

Focal spontaneous regression possible, but rare

Treatment options include laser therapy

Dilated, relatively thick-walled capillaries in the papillary dermis and midreticular dermis

No or limited inflammation and absent hemorrhage

Increased dermal mucin described infrequently

Pigmented purpuric dermatosis

Unilateral nevoid telangiectasia syndrome

Angiokeratoma

No sex predilection

Mainly in adult patients on sun-exposed areas

Dark blue to violaceous papule

Soft and compressible

Usually less than 1 cm in diameter

Solitary lesions predominate

Predilection for the lips, followed by ear, face, and hands

Most commonly asymptomatic, but can be associated with bleeding upon minor trauma

Similar lesions can develop in oral mucosa

No spontaneous regression

No treatment generally required

Treatment options are surgical excision, laser therapy, liquid nitrogen, and sclerosing agents

Pyogenic granuloma may complicate cryosurgery

Dilated and congested vein in the superficial dermis

Lined by a single layer of flat endothelial cells

Perivascular fibrosis occasionally seen

Solar elastosis usually present in the surrounding dermis

Angiokeratoma

All ethnic groups and races can be affected

Equal gender distribution

Incidence varies according to geographical location from 1 in about 1300 (Afro-Caribbeans in the Netherlands Antilles) to 1 in about 40,000 (Northern England)

Skin lesions usually develop in the third decade of life

The majority of patients (95%) develop macular telangiectases, measuring a few millimeters in diameter

Lesions disappear upon pressure

Affected sites most commonly include lips, mouth (oral mucosa), nose, and hands (fingers)

Increase in size and number of the lesions with age

Occasional bleeding can be observed

Painful lesions distinctly uncommon

Skin lesions usually represent a cosmetic defect with no treatment generally required

Laser therapy

Dilatation of postcapillary venules, capillaries, and arterioles in the superficial but also deep dermal vascular plexus

• Thin-walled

• Lined by a single layer of endothelial cells

• Can have convoluted appearance

Deep dermal vessels occasionally display irregularly thickened walls due to proliferation of pericytes

Mild perivascular inflammatory cell infiltrate

Autosomal-dominant mode of inheritance with nearly 100% penetrance by the age of 40 years

The most frequent mutations (about 80%) involve the endogelin ( END ) gene on the long arm of chromosome 9 (9q33-q34.1) and the activin receptor–like kinase 1 ( ALK-1 ) gene on the long arm of chromosome 12 (12q11-q14); much less frequent are mutations in the MADH4 or SMAD4 gene (18q21.2 region) and in yet-to-be-identified genes or gene loci mapped to chromosomes 5 and 8

A combined juvenile polyposis and hereditary hemorrhagic telangiectasia syndrome has been associated with mutations in the SMAD4 gene

Severity of the disease does not correlate with any specific mutation

Generalized essential telangiectasia

Vascular malformation

Female predominance

Usually develops in the fourth decade of life or later

No familial predisposition

Initial presentation most commonly on lower extremities, followed by a slowly, but gradually progressive spread involving the trunk and upper extremities, eventually becoming generalized

Telangiectases can be macular, plaquelike, discrete, or confluent

Generally asymptomatic, occasionally painful, mildly pruritic, and/or with numbness, tingling, or burning sensations

No bleeding disorder

No systemic involvement

Involvement of mucous membranes and conjunctiva rare; rarely accompanied by recurrent bleeding

Association with Graves disease and occurrence in surgical scars reported in isolated cases

Persistent and progressive lesions

Difficult to treat due to widespread distribution

Patients seek treatment mainly due to cosmetic reasons and psychological effects

Treatment options include tetracyclines, acyclovir, topical steroids, with limited success

Laser therapy and intense pulsed-light therapy

Thin-walled, dilated, postcapillary venules in the superficial vascular plexus

Absent or mild perivascular inflammatory cell infiltrate

Hereditary hemorrhagic telangiectasia

Cutaneous collagenous vasculopathy

Telangiectasia macularis eruptive perstans

Male predominance

Middle-aged and elderly patients (from 41 to 80 years)

Telangiectatic macules, frequently symmetrical

Blanching under pressure

Initially on lower extremities with subsequent spreading to trunk and upper extremities

Sparing of mucosal surfaces and nail bed

Asymptomatic, but occasionally mildly pruritic

Can be more prominent with heat and exertion

Seasonal variation of symptoms possible, with occasional worsening during the summer period

No photosensitivity

No concomitant bleeding disorder or connective tissue disease

Familial history generally unremarkable

Lesions remain stable, but may darken over time

No treatment generally necessary

Pulsed dye laser therapy can be beneficial with acceptable cosmetic results

Recurrence of the lesion within the scar after diagnostic biopsy has been reported

Postcapillary venules in the papillary dermis

• Lined by a single layer of flat endothelial cells

• Prominent dilatation

• The walls thickened due to abundant deposition of collagen

Focal splitting and reduplication of the basement membrane

No extravasation of red blood cells and no hemosiderin deposition

No or limited perivascular inflammatory cell infiltrate

Homogeneous eosinophilic material in the thickened walls

• PAS positive and diastase resistant

• Masson trichrome positive

• Reactive with antibodies against type IV collagen and laminin

• Congo red negative

• Ultrastructural analysis demonstrates material to be composed of collagen with abnormal banding pattern (Luse bodies)

Hereditary hemorrhagic telangiectasia

Hereditary benign telangiectasia

Generalized essential telangiectasia

Porphyria and pseudoporphyria

Amyloidosis

Lipoid proteinosis

Atrophie blanche

Solitary angiokeratoma

• The most common variant, representing about 80% of all angiokeratomas

• Wide age distribution, most commonly in the second to fourth decade of life

• Male predominance

Fordyce angiokeratomas

• Predilection for adults/elderly patients

Mibelli angiokeratomas

• Girls between 10 and 15 years predominantly affected

Angiokeratoma corporis diffusum

• Usually before puberty, between the ages of 5 and 10 years

• Males most commonly affected, with more severe and widespread cutaneous involvement

Solitary angiokeratoma

• Sites of predilection are the lower extremities, but any site can be affected, including mucosal surfaces

• Asymptomatic, warty, hyperkeratotic papule or nodule

• Size from 2 to 10 mm in greatest diameter

• Bleeding after minor trauma not infrequent

Fordyce angiokeratomas

• Most commonly on the scrotum, shaft of the penis, or vulva

• Less frequent sites include thighs, abdomen, and groin

• Multiple red-blue papules measuring from 2 to 5 mm

• Congenital occurrence exceptional

• Usually asymptomatic

• Bleeding, pain, pruritus, or burning sensations occasionally present

Mibelli angiokeratomas

• Group of purple macules, warty papules, or nodules

• Size from 2 to 8 mm in diameter

• Predilection for the dorsal parts of the limbs, especially toes, fingers, and interdigital spaces

• Association with acrocyanosis and chilblains not uncommon

• Autosomal-dominant mode of inheritance

Angiokeratoma corporis diffusum

• Widespread purple to dark red papules

• Predilection for “bathing trunk area,” including the lower back, buttocks, penis, scrotum, and inner thighs

• Distribution frequently symmetrical

• The presence of cutaneous vascular lesions in patients with Fabry disease correlates with the severity of the systemic disease

• Initially considered to be a marker of Fabry disease, an X-linked lysosomal storage disease due to α-galactosidase A deficiency

• Similar lesions can also develop in patients with a deficiency of other enzymes, such as β-mannosidase, β-galactosidase, neuraminidase, aspartylglycosaminidase, α-N-acetylgalactosaminidase, or α-L-fucosidase

• Also reported in individuals with no apparent enzyme deficiency

• Associated conditions include Turner syndrome, tuberous sclerosis, Klippel–Trénaunay–Weber syndrome, arteriovenous fistulas, Hodgkin lymphoma

Depends on the clinical setting

Fabry disease may be treated with enzyme replacement therapy

Treatment options include curettage, electrodissection, cryotherapy, laser therapy, and surgical excision

All clinical variants of angiokeratomas share identical histological features

Dilated and blood-filled preexistent vascular channels in the superficial dermis

• Lined by a single layer of endothelial cells

• Thrombosis of vascular spaces not infrequent, may be followed by organization of the thrombus with the formation of papillary endothelial hyperplasia (Masson tumor)

Vascular channels partially or completely surrounded by elongated rete ridges

Epidermal changes include variable degrees of hyperkeratosis

Fordyce angiokeratomas and angiokeratoma corporis diffusum frequently lack associated epidermal proliferation

In patients with Fabry disease, intracytoplasmic lipid vacuoles may be present in endothelial cells, pericytes, vascular smooth muscle cells, fibroblasts, or arrector pili muscles

Verrucous hemangioma

Lichen sclerosus with angiokeratoma-like changes

No sex predilection

Lesions fully developed at birth

Lack of subsequent growth after delivery

Pink to violaceous plaques or nodules, occasionally surrounded by a pale rim and/or covered by multiple tiny telangiectases

Surface ulceration can be present

Most commonly on the head area (including face) and lower extremities, followed by upper extremities

Can be associated with congestive heart failure or thrombocytopenia and coagulopathy, but generally self-limited and not complicated by bleeding diathesis

No treatment generally required unless lesions are function or life threatening

The majority of lesions regress spontaneously within the first 14 to 24 months, leaving residual atrophic skin

Surgical treatment may be necessary in lesions developing complications, like surface ulceration and/or bleeding; other treatments include embolization and systemic steroids

Lobules in the dermis and subcutis, composed of small blood vessels, reminiscent of capillaries

• Lined by a single layer of flat or focally plump endothelial cells, with occasional regular mitoses

• Endothelial cells surrounded by a layer of pericytes

• Basement membrane of endothelial cells initially thin, can become thickened in later stages

Prominent, thin-walled, draining vessels frequently present in the center of the lobules

The involuting central zone is seen in about 50% of the cases with loss of lobules and more prominent fibrosis

Fibrous stroma surrounding the lobules

• Can be prominent, especially in the central parts of the lesion

• Larger vessels corresponding to veins (more common), arteries, and lymphatic-type vessels can also be seen

Arteriovenous fistulae uncommon

Additional changes include

• Areas of hemorrhage and hemosiderin deposition

• Thrombosis of vascular channels

• Dystrophic calcifications

• Extramedullary hematopoiesis

• Atrophy of the overlying epidermis with loss of epidermal appendages

GLUT-1 usually negative, although focal positivity demonstrated in rare cases

Noninvoluting congenital hemangioma

Infantile hemangioma

Equal sex distribution

Fully developed lesions at birth

Solitary, well-demarcated, round to oval, plaquelike lesion

Pink to purple with intermingled areas of pallor and foci of coarse telangiectasia

Frequently surrounded by a pale rim

Usually does not exceed 5 cm in diameter

Warm on palpation

Predilection for head and neck, extremities, and trunk

Association with multiple epidermal cysts and Mongolian spots reported recently

Does not regress spontaneously

Grows proportionally with the child

Treatment may be necessary in large lesions that interfere with function or are life threatening

The treatment includes surgical excision and embolization

Lobules in the dermis and subcutis composed of small vascular channels

• Lined by a single layer of endothelial cells with focal hobnail morphology, lack of nuclear atypia, and absent/exceptional mitotic activity

• Endothelial cells surrounded by one or several layers of pericytes

• Most channels larger than capillaries, but capillary-sized vessels also present

• Vessel walls lack elastic fibers

• Basal membrane can be thick, hyalinized, and multilamellated, but this is generally a focal phenomenon

• Lobules occasionally protrude into larger vein or lymphatic-type vessel, imparting a papillary appearance of the lesion

• Thromboses in different stages of organization

• Center of the lobules contains a draining channel (centrilobular vessel)

  • Thin-walled and stellate-shaped vessel

  • Frequently surrounded by fibrous tissue

  • Continuous with interlobular veins

Stroma in between the lobules contains larger vessels corresponding to veins (more common), arteries, and lymphatic-type vessels; stroma can predominate over lobules in rare instances

Arteriovenous fistulae common (can be demonstrated by elastic stains)

GLUT-1 generally negative

Rapidly involuting congenital hemangioma (RICH)

Infantile hemangioma

Arteriovenous malformations

One of the most common benign vascular proliferations of infancy with an incidence between 5% and 10%

More common in female infants (about 3 : 1)

Predilection for Caucasians

Risk factors include advanced maternal age, multiple gestations, low birth weight, prematurity, preeclampsia, and placenta previa

Generally not present at birth

Starts developing within the first few weeks of life as telangiectatic patch or pale plaque

During the phase of rapid growth the lesions become bright red to purple with raised surface or bluish to skin-colored nodule, usually at the age of about 5 to 9 months

Fully developed lesions generally measure less than 5 cm in greatest diameter

After a short period of minimal change in growth, size, and color, the lesion enters into the phase of regression, becoming softer and associated with the change of color from bright red to purple gray (from 12 months to 5–10 years)

Residual changes include fibrofatty tissue, scarring, and telangiectases

Localized/focal, segmental, or indeterminate variants recognized on the basis of distribution of the lesions

Segmental lesions, encompassing larger anatomical areas, associated with higher incidence of complications (see later)

Associated conditions include

• PHACE syndrome ( p osterior fossa malformations, infantile h emangiomas, a rterial anomalies of the great cerebral vessels, c ardiac defects/coarctation of aorta, e ye anomalies)

• Lesions localized to lumbosacral area have increased risk of underlying developmental abnormalities (e.g., spinal dysraphism, defects of the anorectal and urinary tract)

Most of the lesions will regress spontaneously, although the process might take up to 10 years to complete

No treatment generally required except in lesions that are function or life threatening in which case other treatments, including systemic steroids and more recently propranolol, can be tried

Complications include ulceration, infection, bleeding, disfigurement, and scarring

Features vary depending on the phase

Multilobular proliferation in the dermis and subcutis

• Composed of numerous small vascular spaces, which may not be readily apparent during the initial proliferative phase in which pericytes predominate

• Vessels enlarge and dilate with maturation

• The vessels are lined by plump endothelial cells with frequent mitotic activity, eventually becoming flatter and without mitoses

• All vessels are surrounded by a layer of pericytes

Fibrous septa separating the lobules

• Large feeding arteriole usually seen at the deepest aspect of the proliferation

Additional feature

• Perineural invasion

Older lesions

• Disappearance of vascular lobules

• Fibrosis, which can be prominent

• Fatty metaplasia

Uniformly positive for GLUT-1

Proliferating lesions show coexpression of CD34 and LYVE-1

LYVE-1 negative in involuting lesions

Rapidly involuting congenital hemangioma

Noninvoluting congenital hemangioma

Congenital or acquired

• Most frequent during infancy and childhood

• About 50% develop during the first year of life

• From 60% to 70% develop before the age of 5 years

• Less than 10% occur after the age of 50 years

Male predominance

No racial predisposition

Predilection for extremities, followed by trunk and head and neck

Unusual locations include mucosal surfaces, palms, and perianal skin

Solitary lesions predominate over multifocal lesions

Eruptive variants very rare, usually in immunocompromised patients

Variable clinical presentation, from poorly delineated erythematous or brown-blue macule(s) to dusty red or violaceous, poorly defined, infiltrating plaque(s) with superimposed angiomatous papules to indurated violaceous tumor(s)

Hyperpigmented, linear, or annular variants also reported

Size from 2 to 5 cm

Extensive area can be affected, leading to functional disability and disfiguration

May be associated with hyperhidrosis and hypertrichosis of the affected area

Occasionally painful and tender

Lesions are usually slowly growing, becoming stable in size over time

Exceptional occurrence in pregnancy with regression after delivery, after liver transplantation, in the area of a healed herpes zoster, at the site of bacillus Calmette–Guérin (BCG) vaccination, in a familial setting (monogenic autosomal-dominant predisposition reported in two families), in a patient with neurofibromatosis type I, in an intravenous location, and within a preexistent vascular malformation

Three typical clinical settings

• Without complications

• Associated with Kasabach–Merritt syndrome (consumptive coagulopathy with severe thrombocytopenia and hypofibrinogenemia)

• Without thrombocytopenia but associated with chronic coagulopathy

Spontaneous regression possible but rare, no treatment generally recommended in uncomplicated congenital and early infantile lesions

Surgical excision for smaller lesions, recurrences possible

Diverse drugs, solitary or in combination, including systemic corticosteroids, intralesional steroid injections, interferon-alpha, aspirin, ticlopidine, vincristine, and propranolol, with variable success

Pulsed dye laser and intense pulsed light

Cryotherapy

Disseminated lobules in a “cannonball” distribution

• Most commonly throughout the dermis

• Extension into a superficial fatty tissue rare

• Infiltration into deep subcutis, fascia, or underlying muscle is exceptional

Lobules composed of tufts of convoluted capillaries, typically surrounded by a crescent-shaped empty vascular space(s), corresponding to lymphatic(s)

• Capillary tufts lined by endothelial cells with epithelioid and/or spindle cell morphology, occasionally containing intracytoplasmic hyaline globules

• Capillary tufts separated by slitlike spaces containing erythrocytes

Crescent-shaped or slitlike lymphatic vessels also present within capillary tufts as well as in the dermis between the lobules; the latter can be prominent, simulating lymphangioma

Perilobular fibrosis frequently seen

D2-40 (podoplanin) stains crescent-shaped and slitlike vessels within and surrounding the lobules, as well as lymphatics in the dermis between capillary lobules

Patchy focal staining of capillary tufts with D2-40 (podoplanin) occasionally seen

Focal positivity for LYVE-1

Activating GNA14 mutations recently noted

Glomeruloid hemangioma

Reactive angioendotheliomatosis

Lobular capillary hemangioma

Kaposiform hemangioendothelioma

Nodular Kaposi sarcoma

Typically apparent at birth, but presentation in early childhood not uncommon

About 95% develop on lower extremities

Unusual locations include mucosal surfaces (e.g., glans penis)

Associated conditions include Cobb syndrome (dermatomal distribution of a congenital vascular proliferation associated with meningospinal vascular malformation), Kasabach–Merritt syndrome, and eccrine angiomatous hamartoma

Gradual enlargement with increasing age of the patient

Size between 0.5 and 7 cm

Unilateral lesions predominate, bilateral presentation exceptional

Linear or serpiginous presentation may be the consequence of distribution along Blaschko lines, dermatomes, or the result of genetic mosaicism

Eruptive occurrence of multiple lesions exceptionally reported

Early lesions

• Single soft bluish-red to violaceous plaque, papule, or nodule with irregular borders, nonkeratotic

• Alternatively, grouped plaques with small satellite papule(s)

• Compressible

Older lesions

• Acquire bluish-black keratotic, warty appearance

• Frequently demonstrate lateral spread

• Display partial blanching on compression

Complications include infections, oozing, and bleeding, especially on trauma

Does not regress spontaneously

Complete removal challenging due to the deep extension of the lesion, especially in long-standing lesions

Superficial procedures, like cryotherapy, laser surgery, and electrocautery, usually unsuccessful, invariably leading to recurrences

Deep surgical excision generally necessary

Larger lesions may require multistage surgical procedures

Tendency to recur after incomplete excision

Epidermis displaying variable hyperkeratosis, irregular acanthosis, papillomatosis, and patchy parakeratosis

Ill-defined and poorly circumscribed vascular proliferation

• Infiltration of deep dermis and subcutis

• Involvement of the underlying fascia rare

• Blood vessels display multilamellated basement membrane

Thin-walled blood vessels resembling dilated veins in the papillary and superficial reticular dermis abutting the epidermis

• Lined by flattened endothelium

• Dilated and congested, occasionally thrombosed

• Frequently contain pink proteinaceous material

• Delicate papillary projections protruding into the lumen not uncommon

• Frequently display vertical orientation

Thick-walled, capillary-sized blood vessels in the deeper reticular dermis and subcutis interspersed between the dermal collagen and mature adipocytes

• Congested or with empty lumina

• Formation of clusters and lobules, especially at the dermal–subcutaneous junction

Mild dermal fibrosis, focal deposition of hemosiderin, and mild inflammatory cell infiltrate are additional features

GLUT-1 staining inconsistent, the majority appear to be positive

WT-1 negative in the majority of cases

D2-40 (podoplanin) and Prox1 negative

Angiokeratoma

Infantile hemangioma

Vascular malformation (lymphatic, venous)