Tumors of vascular origin





Benign tumors including reactive vascular proliferations and ectasias


Intravascular Papillary Endothelial Hyperplasia (Masson tumor)


Definition





  • A nonneoplastic, reactive, endothelial proliferation representing an organizing thrombus, characterized by formation of arborizing and interconnecting intravascular papillary cores lined by endothelial cells



Clinical features


Epidemiology





  • Middle-aged adults



  • Slight female predominance



Presentation





  • 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



Prognosis and treatment





  • 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



Pathology


Histology





  • 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



Differential diagnoses





  • Well-differentiated angiosarcoma



  • Lymphangioma


Fig. 1


Intravascular papillary endothelial hyperplasia.

Note interconnecting and arborizing intraluminal papillary projections. Remnants of a preexistent thrombus can be seen at multiple areas.



Fig. 2


Intravascular papillary endothelial hyperplasia.

Papillary projections with cores of eosinophilic material lined by a single layer of bland endothelial cells.



Fig. 3


Intravascular papillary endothelial hyperplasia.

Bland or plump endothelial cells lacking multilayering and mitotic activity.



Fig. 4


Intravascular papillary endothelial hyperplasia.

Extensive hyalinization can be observed in advanced stages.




Reactive Angioendotheliomatosis


Definition





  • A reactive extravascular and/or intravascular proliferation of endothelial cells predominantly within the dermis with occasional involvement of the subcutis



  • Diffuse dermal angiomatosis represents a localized variant of reactive angioendotheliomatosis associated with ischemia



  • Additional comorbidities in a significant proportion of the patients, most frequently systemic diseases



Clinical features


Epidemiology





  • 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




Presentation





  • 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



Prognosis and treatment





  • No specific treatment available



  • The lesions generally resolve after eliminating the underlying cause



  • Recurrence possible



Pathology


Histology





  • 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




Main differential diagnoses





  • Intravascular lymphoma



  • Intravascular histiocytosis



  • Glomeruloid hemangioma



  • Tufted angioma


Fig. 1


Reactive angioendotheliomatosis.

Low-power magnification reveals a multifocal vascular proliferation following the path of the superficial and deep dermal vascular plexus.



Fig. 2


Reactive angioendotheliomatosis.

Closely packed, small, congested, thin-walled vascular channels, each surrounded by a layer of pericytes.



Fig. 3


Reactive angioendotheliomatosis.

Intravascular and extravascular proliferation of endothelial cells with no significant cytological atypia. Solid areas with inconspicuous lumina can be seen.



Fig. 4


Reactive angioendotheliomatosis.

Inflammation, if present, is mild and mitotic activity is low.




Glomeruloid Hemangioma


Definition





  • A benign, reactive, dermal, vascular proliferation characterized by aggregates or tufts of capillaries within dilated vascular spaces forming an organoid pattern reminiscent of renal glomeruli



  • A strong association exists with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome and multicentric Castleman disease



Clinical features


Epidemiology





  • Present in about 3% of patients with POEMS syndrome



  • No sex predisposition



  • Very rare cases reported in patients without POEMS syndrome



Presentation





  • 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



Prognosis





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



Pathology


Histology





  • 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



Main differential diagnoses





  • Papillary hemangioma



  • Intravascular pyogenic granuloma



  • Intravascular papillary endothelial hyperplasia (Masson tumor)



  • Tufted angioma


Fig. 1


Glomeruloid hemangioma.

Proliferation of capillary tufts within dilated vascular spaces can be appreciated throughout the dermis. Note their resemblance to renal glomeruli.



Fig. 2


Glomeruloid hemangioma.

Closely packed capillaries with areas of intraluminal thrombi.



Fig. 3


Glomeruloid hemangioma.

Endothelial cells are bland and there is no multilayering.



Fig. 4


Glomeruloid hemangioma.

Rare inflammatory cells can be seen within proliferating capillaries.




Papillary Hemangioma


Definition





  • Benign vascular tumor composed of dilated vascular channels containing intravascular papillae with stromal cores and stalks



  • Not associated with POEMS syndrome or Castleman disease



  • It has been suggested that these lesions represent solitary examples of glomeruloid hemangioma



Clinical features


Epidemiology





  • 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



Presentation





  • Solitary skin-colored to bluish papule or nodule



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



Prognosis and treatment





  • Complete excision curative



  • Local recurrence exceptional



Pathology


Histology





  • 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




Immunohistochemistry/special stains





  • 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



Differential diagnoses





  • Glomeruloid hemangioma



  • Intravascular pyogenic granuloma



  • Intravascular papillary endothelial hyperplasia (Masson tumor)


Fig. 1


Papillary hemangioma.

A well-demarcated, dermal, vascular proliferation is seen containing numerous papillary intraluminal projections.



Fig. 2


Papillary hemangioma.

Numerous intravascular papillae with stromal cords and stalks are seen within dilated vascular spaces. Areas of thrombosis can also be appreciated (upper right).



Fig. 3


Papillary hemangioma.

Dilated vascular channels with thrombus (left) and numerous intravascular papillary projections (right).



Fig. 4


Papillary hemangioma.

Intravascular papillae with stromal cords are lined by a single layer of bland endothelial cells.



Fig. 5


Papillary hemangioma.

Papillary projections—higher magnification.




Nevus Flammeus


Definition





  • Nevus flammeus is, in its broadest sense, an expression used unrestrictedly for congenital vascular malformations, including port wine stain and salmon patch



  • Lesions similar to salmon patch have also been designated as angel kiss, stork bite, nevus flammeus neonatorum, nevus simplex, midline nevus flammeus, nuchal rash, and nuchal telangiectatic nevus



  • Port wine stain generally shows progressive growth with the age of the patient and can be associated with various syndromes (see later)



  • Salmon patch has a tendency to regress within the first years of life and is rarely associated with a particular syndrome



  • Nevus flammeus has frequently been used interchangeably and/or synonymously with port wine stain



Clinical features


Epidemiology





  • 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




Presentation





  • 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




Prognosis and treatment





  • 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



Pathology


Histology





  • 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



Main differential diagnosis





  • Clinical presentation typical with generally no relevant differential diagnosis


Fig. 1


Nevus flammeus.

The lesion is characterized by increased number of capillaries and postcapillary venules in the dermis. Dilated vascular lumina are common, especially in established lesions.



Fig. 2


Nevus flammeus.

Dilated thin-walled vascular channels in the superficial dermis.



Fig. 3


Nevus flammeus.

Increased number of capillaries in the dermis lined by bland endothelial cells and surrounded by a layer of pericytes.



Fig. 4


Nevus flammeus.

Vertical arrangement of capillaries and postcapillary venules is seen in this example. Note the absence of inflammation around the blood vessels.




Cutis Marmorata Telangiectatica Congenita


Definition





  • A congenital vascular abnormality of unknown etiology characterized clinically by reticulate erythema, telangiectasia, skin atrophy, and/or skin ulceration



Clinical features


Epidemiology





  • 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)



Presentation





  • 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





Prognosis and treatment





  • 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



Pathology


Histology





  • 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



Main differential diagnoses





  • Physiological cutis marmorata



  • Persistent cutis marmorata, also associated with genetic syndromes



  • Livedo racemosa



  • Diffuse phlebectasia (Bockenheimer syndrome)



  • Klippel–Trénaunay syndrome



  • Neonatal lupus erythematosus



Spider Nevus


Definition





  • A vascular lesion composed of a central arteriole from which thin radiating vessels originate, thereby mimicking a spider



  • Synonyms include spider angioma, nevus araneus, vascular spider, arterial spider



Clinical features


Epidemiology





  • 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)



Presentation





  • 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



Prognosis and treatment





  • No treatment generally required



  • Treatment options include pulsed dye laser, electrocoagulation



Pathology


Histology





  • Dilatation of preexisting blood vessels in the superficial and middermis



Main differential diagnoses





  • Cherry angioma



  • Angioma serpiginosum



  • Angiokeratoma



  • Disseminated essential telangiectasia



Angioma Serpiginosum


Definition





  • An acquired vascular lesion, most likely a vascular malformation, characterized by dilated and thick-walled capillaries in the papillary and midreticular dermis



Clinical features


Epidemiology





  • Strong female predominance (about 90%)



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



Presentation





  • 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




Prognosis and treatment





  • No treatment usually necessary



  • Focal spontaneous regression possible, but rare



  • Treatment options include laser therapy



Pathology


Histology





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



  • No or limited inflammation and absent hemorrhage



  • Increased dermal mucin described infrequently



Main differential diagnoses





  • Pigmented purpuric dermatosis



  • Unilateral nevoid telangiectasia syndrome



  • Angiokeratoma


Fig. 1


Angioma serpiginosum.

The entity is characterized by aggregates of dilated and thick-walled capillaries in the superficial dermis. Extravasation of erythrocytes is absent, and there is no inflammation.




Venous Lake


Definition





  • A vascular lesion characterized by dilated and congested veins in the superficial dermis, usually in the background of solar elastosis



Clinical features


Epidemiology





  • No sex predilection



  • Mainly in adult patients on sun-exposed areas



Presentation





  • 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



Prognosis and treatment





  • No spontaneous regression



  • No treatment generally required



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



  • Pyogenic granuloma may complicate cryosurgery



Pathology


Histology





  • 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



Main differential diagnoses





  • Angiokeratoma


Fig. 1


Venous lake.

A dilated and congested vein in the superficial dermis.



Fig. 2


Venous lake

—higher magnification.



Fig. 3


Venous lake.

Dilated vein lined by a single layer of bland endothelial cells.




Hereditary Hemorrhagic Telangiectasia (Osler–Weber–Rendu syndrome)


Definition





  • An autosomal-dominant disorder, characterized by the presence of telangiectases and arteriovenous malformations involving skin, mucosal surfaces, and visceral organs



  • Essential diagnostic criteria comprise (three or more = definite, two = possible, less than two = unlikely)




    • Spontaneous and recurrent epistaxis



    • Mucocutaneous telangiectases, particularly involving the lips, tongue, oral cavity, fingers, and nose



    • Internal arteriovenous malformations, including pulmonary, cerebral, hepatic, gastrointestinal, and spinal



    • First-degree relative with the disease, according to these criteria




Clinical features


Epidemiology





  • 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)



Presentation





  • 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



Prognosis and treatment





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



  • Laser therapy



Pathology


Histology





  • 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



Genetic profile





  • 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



Main differential diagnoses





  • Generalized essential telangiectasia



  • Vascular malformation



Generalized Essential Telangiectasia


Definition





  • An acquired condition of unknown etiology characterized by progressive telangiectasia in a widespread anatomical distribution, generally unaccompanied by bleeding disorder or systemic involvement



Clinical features


Epidemiology





  • Female predominance



  • Usually develops in the fourth decade of life or later



  • No familial predisposition



Presentation





  • 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



Prognosis and treatment





  • 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



Pathology


Histology





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



  • Absent or mild perivascular inflammatory cell infiltrate



Main differential diagnoses





  • Hereditary hemorrhagic telangiectasia



  • Cutaneous collagenous vasculopathy



  • Telangiectasia macularis eruptive perstans



Cutaneous Collagenous Vasculopathy


Definition





  • An idiopathic form of microangiopathy characterized by dilatation of postcapillary venules in the papillary dermis with prominent collagen deposition within their walls



Clinical features


Epidemiology





  • Male predominance



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



Presentation





  • 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



Prognosis and treatment





  • 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



Pathology


Histology





  • 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



Immunohistochemistry/special stains





  • 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)




Main differential diagnoses





  • Hereditary hemorrhagic telangiectasia



  • Hereditary benign telangiectasia



  • Generalized essential telangiectasia



  • Porphyria and pseudoporphyria



  • Amyloidosis



  • Lipoid proteinosis



  • Atrophie blanche


Fig. 1


Cutaneous collagenous vasculopathy.

Numerous small postcapillary venules with thickened, brightly eosinophilic vessel walls are present in the papillary dermis. This example does not feature vascular dilatation.



Fig. 2


Cutaneous collagenous vasculopathy.

A single postcapillary venule with abnormal collagen deposition in the vessel wall is seen in this photo.



Fig. 3


Cutaneous collagenous vasculopathy.

Another postcapillary venule with thickened, brightly eosinophilic wall. Note the absence of red blood cell extravasation and inflammation.




Angiokeratoma


Definition





  • A group of unrelated disorders having in common dilated preexistent vascular channels in the papillary dermis, usually but not always accompanied by secondary epidermal changes



  • Four clinical variants can be distinguished: solitary, Fordyce and Mibelli angiokeratomas, and angiokeratoma corporis diffusum



Clinical features


Epidemiology





  • 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




Presentation





  • 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




Prognosis and treatment





  • 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



Pathology


Histology





  • 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



Main differential diagnoses





  • Verrucous hemangioma



  • Lichen sclerosus with angiokeratoma-like changes


Fig. 1


Angiokeratoma.

Numerous dilated, congested, thin-walled vascular channels in the papillary dermis. The epidermis appears acanthotic and hyperkeratotic, and there is often crusting. A deeper dermal component is not seen.



Fig. 2


Angiokeratoma.

Dilated vascular channels are partially surrounded by elongated rete ridges. Focal areas of thrombosis are frequently seen (right).



Fig. 3


Angiokeratoma.

Vascular channels are lined by a single layer of bland endothelial cells.




Rapidly Involuting Congenital Hemangioma


Definition





  • A vascular proliferation of intrauterine onset, fully developed at birth with subsequent rapid involution over the first 2 years of life



  • Rarely, after initial period of rapid involution, the lesion remains stable, thus displaying overlapping features with a noninvoluting congenital hemangioma (see later)



  • Distinction between rapidly involuting and noninvoluting congenital hemangioma can be difficult on histological grounds alone, and close clinicopathological correlation, supplemented by additional imaging studies, is necessary to adequately characterize the lesion



Clinical features


Epidemiology





  • No sex predilection



Presentation





  • 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



Prognosis and treatment





  • 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



Pathology


Histology





  • 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




Immunohistochemistry/special stains





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



Main differential diagnoses





  • Noninvoluting congenital hemangioma



  • Infantile hemangioma


Fig. 1


Rapidly involuting congenital hemangioma.

Low-power magnification typically reveals lobular proliferation of capillaries throughout the dermis. Notice also the presence of dilated lymphatic-type blood vessels in the dermis.



Fig. 2


Rapidly involuting congenital hemangioma.

Early lesions are characterized by more solid proliferation of endothelial cells.



Fig. 3


Rapidly involuting congenital hemangioma.

Low-power magnification of another lesion composed of lobules of endothelial cells. Vascular nature of the proliferation in early stages might not be readily apparent.

(Courtesy of Tricia Peters, Houston, Texas.)



Fig. 4


Rapidly involuting congenital hemangioma.

As the lesion evolves, vascular lumina become readily apparent. Note also solid areas within the lobules.

(Courtesy of Tricia Peters, Houston, Texas.)



Fig. 5


Rapidly involuting congenital hemangioma.

Higher magnification revealing proliferation of bland endothelial cells in the center of the lobule.

(Courtesy of Tricia Peters, Houston, Texas.)



Fig. 6


Rapidly involuting congenital hemangioma.

In contrast to infantile hemangioma, GLUT-1 is negative in rapidly involuting congenital hemangiomas.

(Courtesy of Tricia Peters, Houston, Texas.)




Noninvoluting Congenital Hemangioma


Definition





  • A vascular proliferation that starts to grow in utero, is fully developed at birth, increases proportionally with the child’s growth, and does not regress spontaneously



Clinical features


Epidemiology





  • Equal sex distribution



  • Fully developed lesions at birth



Presentation





  • 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



Prognosis and treatment





  • 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



Pathology


Histology





  • 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)



Immunohistochemistry/special stains





  • GLUT-1 generally negative



Main differential diagnoses





  • Rapidly involuting congenital hemangioma (RICH)



  • Infantile hemangioma



  • Arteriovenous malformations


Fig. 1


Noninvoluting congenital hemangioma.

Low-power magnification reveals a lobular vascular proliferation in the dermis with extension into the subcutis. Note variation in the size of the blood vessels within the lobules.



Fig. 2


Noninvoluting congenital hemangioma.

The lobules are often composed of capillaries but also of larger and sometimes thicker blood vessels. Large blood vessels with features of arteries, veins, and lymphatics are present in between the lobules.



Fig. 3


Noninvoluting congenital hemangioma.

Another area with lobular proliferation composed of different types of blood vessels.



Fig. 4


Noninvoluting congenital hemangioma.

In this example, lymphatic-type blood vessels are seen in between vascular lobules.



Fig. 5


Noninvoluting congenital hemangioma.

Proliferation of different types of blood vessels closely resembles vascular malformation.






Capillary hemangioma and its variants


Infantile Hemangioma


Definition





  • A vascular proliferation starting after birth characterized by a rapidly progressive growth (proliferative phase), followed by a short period of minimal change in growth, color, and size (plateau phase), subsequently entering into the phase of regression (involutional phase), eventually leaving residual fibrofatty tissue, scarring, and telangiectatic skin



  • Synonyms include juvenile hemangioma, strawberry nevus, and previously infantile hemangioendothelioma (no longer used in this context)



Clinical features


Epidemiology





  • 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



Presentation





  • 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)




Prognosis and treatment





  • 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



Pathology


Histology





  • 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




Immunohistochemistry/special stains





  • Uniformly positive for GLUT-1



  • Proliferating lesions show coexpression of CD34 and LYVE-1



  • LYVE-1 negative in involuting lesions



Main differential diagnoses





  • Rapidly involuting congenital hemangioma



  • Noninvoluting congenital hemangioma


Fig. 1


Infantile hemangioma

—proliferative phase. This phase is characterized by florid proliferation of capillaries. Endothelial cells form solid aggregates, making vascular lumina difficult to appreciate.



Fig. 2


Infantile hemangioma

—proliferative phase. Higher magnification depicting solid proliferation of endothelial cells.



Fig. 3


Infantile hemangioma

—proliferative phase. Proliferating endothelial cells are seen infiltrating arrector pili muscle.



Fig. 4


Infantile hemangioma

—proliferative phase. Perineural infiltration is commonly present.



Fig. 5


Infantile hemangioma

—regressing phase. Low-power magnification of a regressing infantile hemangioma. Note distinctive nodular arrangement of capillaries and fibrosis within the nodule.



Fig. 6


Infantile hemangioma

—regressing phase. This example reveals lobular proliferation of capillaries in between skeletal muscle fibers and associated fibroplasia.



Fig. 7


Infantile hemangioma

—regressing phase. Progressive fibrosis in regressing infantile hemangioma is associated with disappearance of vascular lobules.



Fig. 8


Infantile hemangioma

—regressing phase. Nearly completely regressed infantile hemangioma with prominent fibrosis.



Fig. 9


Infantile hemangioma.

GLUT-1 is consistently positive in infantile hemangiomas, representing an important aid in recognizing the entity.




Tufted Angioma


Definition





  • A benign vascular proliferation characterized by predominantly dermal lobules of convoluted capillary tufts in a cannonball distribution; each lobule is surrounded at the periphery by crescentlike dilated lymphatics



  • An overlap with kaposiform hemangioendothelioma has been suggested



  • Synonyms include tufted angioblastoma of Nakagawa, juvenile tufted angioma, and progressive capillary hemangioma



Clinical features


Epidemiology





  • 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



Presentation





  • 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




Prognosis and treatment





  • 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



Pathology


Histology





  • 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



Immunohistochemistry/special stains





  • 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



Genetic profile





  • Activating GNA14 mutations recently noted



Main differential diagnoses





  • Glomeruloid hemangioma



  • Reactive angioendotheliomatosis



  • Lobular capillary hemangioma



  • Kaposiform hemangioendothelioma



  • Nodular Kaposi sarcoma


Fig. 1


Tufted angioma.

A lobular vascular proliferation is present throughout the dermis with a typical “cannonball” appearance. Note crescentlike lymphatics at the periphery of tumor lobules. Dilated lymphatics are also seen in the intervening dermis.



Fig. 2


Tufted angioma.

Variable-sized lobules composed of tufts of capillaries.



Fig. 3


Tufted angioma.

Vascular channels are lined by a single layer of endothelial cells. The spindle-shaped cells seen in the background represent pericytes.



Fig. 4


Tufted angioma.

Lobules of capillaries are typically surrounded by a crescentlike lymphatics.



Fig. 5


Tufted angioma.

Intracytoplasmic hyaline globules can occasionally be found within endothelial cells.




Verrucous Venous Malformation (Verrucous Hemangioma)


Definition





  • A congenital vascular proliferation, a malformation, involving the dermis, extending into the subcutis, composed of dilated blood vessels resembling veins in the superficial dermis, capillaries and thick-walled blood vessels in the deep dermis and subcutis; it is associated with marked hyperkeratosis, acanthosis, and papillomatosis of the epidermis



Clinical features


Epidemiology





  • 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



Presentation





  • 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



Prognosis and treatment





  • 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



Pathology


Histology





  • 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



Immunohistochemistry/special stains





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



  • WT-1 negative in the majority of cases



  • D2-40 (podoplanin) and Prox1 negative



Main differential diagnoses





  • Angiokeratoma



  • Infantile hemangioma



  • Vascular malformation (lymphatic, venous)


Fig. 1


Verrucous venous malformation.

Distinguishing low-power features are marked hyperkeratosis, acanthosis, and papillomatosis of the epidermis, along with ill-defined vascular proliferation, typically extending into the deep dermis and subcutis.



Fig. 2


Verrucous venous malformation.

Thin-walled, dilated blood vessels in the papillary dermis resembling dilated veins are seen abutting into the epidermis. Superficial component displays morphological overlap with angiokeratoma.



Fig. 3


Verrucous venous malformation.

A lobular arrangement of capillaries is frequently present at the dermal–subcutaneous junction.



Fig. 4


Verrucous venous malformation.

Higher magnification of the deep component in the subcutis.




Cherry Angioma


Definition





  • An acquired vascular proliferation, characterized by proliferation of dilated capillaries and postcapillary venules in the superficial dermis



  • Represents a benign vascular tumor and not a vascular malformation



  • Also designated as cherry hemangioma, senile angioma, senile hemangioma, or Campbell de Morgan spot



Clinical features


Epidemiology





  • Usually start developing after the third decade of life




    • In 5% of adolescents



    • In 75% of adults over the age of 75 years




  • Their number increases with the age of the patient



Presentation





  • Asymptomatic, multiple well-circumscribed, flat, erythematous macules or dome-shaped, bright red papules



  • Size from 1 to 5 mm



  • Generally asymptomatic



  • Bleeding after trauma not uncommon



  • Predominantly located on upper extremities and trunk



  • Rare sites include face, hands, and feet



  • Associated conditions with multiple cherry angiomas include pregnancy, liver transplantation, graft versus host disease, immunosuppression due to cyclosporine therapy, primary biliary cholangitis exposure to chemicals (bromides, sulfur mustard gas), familial nevus flammeus, familial cerebral cavernous malformations, and Fabry disease



  • Eruptive occurrence reported after treatment of vitiligo by topical nitrogen mustard within and around the affected area



  • Colonization by intravascular, large, B-cell lymphoma reported in exceptional cases



Prognosis and treatment





  • No treatment generally necessary



  • Treatment options include, mainly due to cosmetic reasons or to prevent bleeding, laser therapy, electrosurgery, curettage



Pathology


Histology





  • Newly formed capillaries and postcapillary venules in the superficial dermis, with a lobular pattern



  • Vascular lumina initially narrow, eventually become dilated



  • Lined by a single layer of endothelial cells, sometimes protruding into the lumina



Main differential diagnoses





  • Lobular capillary hemangioma



  • Cirsoid aneurysm


Fig. 1


Cherry angioma.

This entity is characterized by increased numbers of capillaries and postcapillary venules in the papillary dermis, frequently arranged in a lobular pattern. Note the absence of perivascular inflammation.



Fig. 2


Cherry angioma.

Higher magnification depicting proliferation of capillaries and postcapillary venules in the papillary dermis.



Fig. 3


Cherry angioma.

Another area depicting hyalinization of vessel walls.




Lobular Capillary Hemangioma (Pyogenic Granuloma)


Definition





  • A vascular proliferation composed of capillaries and small veins, in a lobular pattern, admixed with variably cellular collagenous stroma



  • Most likely represents a neoplastic process with extensive secondary changes



  • Variants include pyogenic granuloma developing during pregnancy (granuloma gravidarum), subcutaneous or deep pyogenic granuloma, and intravenous pyogenic granuloma



Clinical features


Epidemiology





  • Wide age distribution, predominantly in the second and third decade of life



  • About 40% of the lesions develop before the age of 5 years



  • Congenital occurrence exceptional



  • Slight male predominance for cutaneous pyogenic granulomas; mucosal and intravascular lesions show predilection for females (F:M, 2 : 1)



  • Granuloma gravidarum develops in about 2% of the pregnancies



Presentation





  • Solitary pedunculated or polypoid red or violaceous papule or nodule



  • Frequently ulcerated with related bleeding



  • Multiple or eruptive occurrence unusual




    • Grouped lesions over localized area



    • Widely disseminated lesions




  • Rapid initial growth within the first few weeks



  • Size up to 2 cm in maximum diameter; giant variants measuring several centimeters in diameter also reported



  • Cutaneous lesions predominate over mucosal sites (86% and 14%, respectively) with predilection for the trunk, head and neck area, and extremities, including periungual tissues and nail bed



  • Lesions on the nail bed and periungual tissue can be extremely painful



  • Granuloma gravidarum most commonly develops on gingival mucosa; other mucosal sites and skin can also be affected



  • Intravenous pyogenic granuloma shows a predilection for the neck and upper extremities



  • Deep/subcutaneous pyogenic granulomas lack surface changes and present as a nodular proliferation



  • Pyogenic granuloma can develop within a preexisting vascular condition




    • Port wine stain, unilateral dermatomal superficial telangiectasia, arteriovenous malformation, or spider angioma




  • Associated conditions (might be coincidental)




    • Disseminated eruptive pyogenic granulomas: hematological malignancies and metastatic melanoma



    • Giant pyogenic granuloma: HIV infection, pregnancy, graft versus host disease, previous trauma or burns



    • Deep pyogenic granuloma: antiphospholipid syndrome




  • Suggested predisposing factors




    • Local trauma, chronic irritation, drugs (retinoids, antiretroviral and antineoplastic drugs), hormones (estrogens), infections, burns, and inflammatory systemic diseases (sarcoidosis, psoriasis, seronegative spondylarthritis, rheumatoid arthritis)




Prognosis and treatment





  • Spontaneous regression uncommon, the exception being granuloma gravidarum



  • Recurrences frequent, especially in adolescents and young adults



  • Recurrences can develop rarely in the form of multiple satellite lesions, usually on the trunk, and especially in children



  • Pyogenic granuloma on the nail can be associated with irreversible damage of the nail plate



  • Treatment options include shave excision, conservative local excision, curettage, electrocautery, topical application of imiquimod, local injection(s) of steroids, pulsed dye laser



Pathology


Histology





  • Proliferation of capillaries and small veins in the dermis or subepithelial stroma, usually in a lobular pattern




    • Vascular lobules set in an edematous/myxoid/collagenous stroma



    • Individual lobules separated by fibrous septa




  • Vascular lumina lined by a single layer of endothelial cells




    • Bland, plump, and rarely focally epithelioid, especially in mucosal lesions



    • Regular mitoses frequent



    • Degenerative cytological atypia occasionally present




  • A “feeding” vessel with muscular wall, usually a small artery accompanied by a vein(s), is seen extending into the base of the lesion from the subcutis



  • Additional changes




    • Inflammatory cell infiltrate composed of neutrophils, histiocytes, lymphocytes, and plasma cells can be prominent but usually restricted to the area of ulceration



    • Surface ulceration



    • The epidermis is often hyperplastic and forms a collarette at the lateral border(s) of the lesion



    • Rarely, extramedullary hematopoiesis, metaplastic ossification, and intravascular papillary endothelial hyperplasia may be seen




  • Intravenous and deep/subcutaneous pyogenic granuloma




    • Lack of inflammation within the lesion




  • Intravenous pyogenic granuloma




    • Usually attached to the wall of the vessel by a stalk



    • Polypoid protrusion into the lumen common




  • Recurrent pyogenic granuloma and satellite lesions




    • Frequently show extension into the subcutis



    • The lobular architecture of the vascular proliferation can be blurred or absent




Genetic profile





  • RAS or BRAF activating mutations have been noted in some cases



Main differential diagnoses





  • Granulation tissue



  • Infantile hemangioma



  • Bacillary angiomatosis


Fig. 1


Lobular capillary hemangioma.

Polypoid lobular proliferation of capillaries is present in the dermis.



Fig. 2


Lobular capillary hemangioma.

A more typical presentation with a polypoid crusted lesion. Note extension into the subcutis, a feature often associated with local recurrence.



Fig. 3


Lobular capillary hemangioma.

Individual lobules are separated by fibrous septa. Endothelial cells may be prominent but are usually bland.



Fig. 4


Lobular capillary hemangioma.

Plump nonatypical endothelial cells. Brisk mitotic activity is common.



Fig. 5


Lobular capillary hemangioma.

In this example, endothelial cells display a more solid growth pattern with poorly defined vascular lumina. Tumor cells often display a single nucleolus.



Fig. 6


Lobular capillary hemangioma.

A feeding vessel with thickened wall is usually present at the base of the tumor lobule.



Fig. 7


Lobular capillary hemangioma

—an intravenous proliferation is seen in this example.



Fig. 8


Lobular capillary hemangioma

—intravenous occurrence, higher magnification. The vessel wall (right) is often prominently attenuated, and the intravascular location may be missed.




Cavernous Hemangioma (Including Sinusoidal Hemangioma)


Definition





  • A vascular proliferation in the dermis/subcutis characterized by numerous large, dilated, and variably thickened blood-filled vascular channels lined by flattened endothelial cells



  • Some of the lesions likely represent a form of vascular (venous) malformation, and there is overlap with noninvoluting congenital hemangioma



  • Sinusoidal hemangioma represents a histological subtype



Clinical features


Epidemiology





  • Equal gender distribution



  • More common in neonates and children, can be present at birth



  • Sinusoidal hemangioma shows predilection for middle-aged females



Presentation





  • Blue or violaceous soft nodules



  • Predilection for head and neck area as well as limbs



  • Associated conditions include Maffucci syndrome (cavernous hemangiomas, enchondromas, and increased risk of developing chondrosarcoma), blue rubber bleb nevus syndrome (hemangiomas in the gastrointestinal tract, skin, liver, and central nervous system), and Kasabach–Merritt syndrome (consumption coagulopathy)



  • Sinusoidal hemangioma




    • Wide anatomical distribution, but most commonly occurs on the limbs and trunk (particularly within the breast), followed by scalp



    • Lesions usually small, from 1 to 3.5 cm, but giant variants measuring over 10 cm in diameter also reported



    • An association with a lipoma reported recently




Prognosis and treatment





  • Does not show tendency to regress spontaneously



  • Does not recur after complete excision



Pathology


Histology





  • Large, dilated, and congested irregular vascular channels in the dermis and subcutis



  • Lined by a single layer of flattened endothelial cells




    • No atypia of endothelial cells



    • Mitoses generally absent




  • The walls of vascular channels usually thin, but an admixture with thicker walls not uncommon



  • Lobular architecture generally not seen



  • Additional changes include




    • Variably intense mononuclear inflammatory cell infiltrate



    • Dystrophic calcification(s)



    • Features of capillary hemangioma, especially in the superficial parts of the lesion




  • Sinusoidal hemangioma




    • Predominantly lobular proliferation in the dermis/subcutis, but areas of infiltrative growth not uncommon (especially in the breast)



    • Large, dilated, and interconnected thin-walled vascular channels, usually separated by inconspicuous and scant stroma, imparting a so-called “back-to-back” or “sinusoidal” appearance of vascular channels



    • Pseudopapillary intraluminal projections lined by endothelial cells




      • Consequence of cross-sectioning




    • Vascular spaces lined by flat endothelial cells




      • Occasionally displaying mild hyperchromasia



      • Mitotic activity absent




    • Regressive changes frequent and include




      • Thrombosis in different stages of organization



      • Collagen hyalinization



      • Calcification and metaplastic ossification





Main differential diagnoses





  • Sinusoidal hemangioma can be confused with well-differentiated angiosarcoma


Fig. 1


Cavernous hemangioma.

Nonlobular, poorly demarcated proliferation of thin-walled, dilated vascular channels lined by flattened endothelium is typically present in the dermis.



Fig. 2


Cavernous hemangioma.

Numerous dilated and variably thickened vascular channels lined by bland endothelial cells represent the hallmark of the entity.



Fig. 3


Cavernous hemangioma.

Lobular architecture is generally not seen. Vascular spaces are separated by scant stroma.




Arteriovenous Hemangioma


Definition





  • A vascular malformation characterized by an admixture of thin- and thick-walled blood vessels



  • Also designated as cirsoid aneurysm and acral arteriovenous tumor



Clinical features


Epidemiology





  • Equal sex distribution



  • Adults in their fifth and sixth decade of life, congenital occurrence rare



Presentation





  • Small, reddish or bluish papule of less than 1 cm in diameter



  • Recurrent bleeding not uncommon, may on occasion be painful



  • Solitary lesions predominate



  • Multiple lesions can present in an eruptive pattern (agminate distribution)



  • Predilection for the head and neck, followed by extremities



  • Mucosal sites can also be affected (oral mucosa, vulva)



  • Giant variants measuring up to 10 cm in diameter rare



  • Occurrence within pyogenic granuloma, epidermal nevus syndrome, nevus flammeus in patients with Sturge–Weber syndrome, and verruciform xanthoma has rarely been reported



  • Appears to be more frequent in patients with chronic liver disease and liver cirrhosis



Prognosis and treatment





  • Local excision is curative



Pathology


Histology





  • Well-circumscribed, nonencapsulated vascular proliferation in the dermis or submucosa, with possible extension into the subcutaneous fatty tissue



  • Admixture of thick- and thin-walled vascular channels




    • Thick-walled vessels resemble arteries, but well-delineated internal elastic lamina is frequently absent or nondetectable; thus the more appropriate designation is venous hemangioma in such an example



    • Well-formed arteriovenous anastomoses can be detected in about 25% of cases




  • Lined by a single layer of endothelial cells



  • Ascending small muscular artery (feeding vessel), typically coiled, can be found originating in the subcutis/deep dermis, but deeper sections may be required



  • Additional features




    • Intraluminal microthrombi



    • Dystrophic calcification



    • Inflammatory cell infiltrate, predominantly composed of lymphocytes




Genetic profile





  • Activating PIK3CA mutations can be present



  • Activating MAP2K1 mutations reported in arteriovenous malformation



Immunohistochemistry/special stains





  • Stains for elastic fibers may be necessary to demonstrate small arteries within the lesion


Fig. 1


Arteriovenous hemangioma.

Well-circumscribed and nonencapsulated vascular proliferation in the dermis. Thick vascular walls can be appreciated.



Fig. 2


Arteriovenous hemangioma.

Thick-walled vessels resemble arteries and veins.



Fig. 3


Arteriovenous hemangioma

—higher magnification.




Microvenular Hemangioma


Definition





  • A benign vascular proliferation composed of haphazardly growing and irregularly branching venules in the background of a collagenous or sclerotic stroma



Clinical features


Epidemiology





  • Young to middle-aged adults



  • Most commonly in the third decade of life (mean age 29.2 years, age range 5–64 years)



  • Occurrence in children rare



  • Slight female predominance (F:M, 1.2 : 1)



  • Predilection for trunk, followed by extremities and head and neck



  • Comorbidities in more than 10% of cases and include acute myelogenous leukemia, asthma, hypertension, hypothyroidism, POEMS syndrome, and Wiskott–Aldrich syndrome



  • A rare association with the use of oral contraceptives has been reported



Presentation





  • Solitary lesions most common (about 80%), slowly growing



  • Multiple lesions rare (about 20%), can develop simultaneously or successively in the same anatomical region or in different regions



  • Eruptive variants characterized by rapid development and wide distribution of lesions



  • Red/erythematous, violaceous or brown macule(s), papule(s), or nodule(s)



  • Size from 0.4 to 3 cm (mean 1.3 ± 0.7 cm, median 1 cm)



  • Asymptomatic in majority of lesion(s), but can be itchy and painful



Prognosis and treatment





  • Solitary lesions are often self-limiting



  • Complete excision curative, recurrences distinctly uncommon



  • Multiple or eruptive lesions can be persistent and difficult to treat



Pathology


Histology





  • Poorly circumscribed proliferation in the dermis



  • Irregularly sized and haphazardly branching venules lined by a single layer of flattened endothelial cells




    • No cytological atypia



    • Endothelial cells can be plump on occasion, protruding into the lumina



    • No or limited mitotic activity



    • Vascular lumina collapsed, inconspicuous or contain red blood cells



    • Endothelial cells surrounded by a peripheral layer of pericytes




  • Infiltration of arrector pili muscle typically presents in the majority of cases, but multiple sections can be required to demonstrate this phenomenon



  • Intervening stroma variably collagenized or sclerotic



  • No extravasation of erythrocytes



  • No hemosiderin deposition



  • Minimal inflammatory cell infiltrate composed predominantly of lymphocytes occasionally present



Main differential diagnoses





  • Reactive angioendotheliomatosis



  • Hobnail hemangioma



  • Tufted hemangioma



  • Kaposi sarcoma



  • Angiosarcoma, well differentiated


Fig. 1


Microvenular hemangioma.

Poorly circumscribed vascular proliferation in the dermis.

Oct 29, 2019 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Tumors of vascular origin
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